Jan Terje Andersen

• Lippold, Steffen; Chang, Kelvin; Dürkoop, Mirjam; Andersen, Jan Terje; Yang, Feng & Schlothauer, Tilman (2026). Development of single-chain C1q affinity chromatography–mass spectrometry for the glycoform-resolved characterization of low-affinity immunoglobulin G interactions. mAbs. ISSN 1942-0862. 18(1). doi: 10.1080/19420862.2026.2687922. Full text in Research Archive
• Felice, Sofia De; Buratto, Christian; Savio, Alessia; Morbidelli, Maria; Papini, Emanuele & Acquasaliente, Laura [Show all 12 contributors for this article] (2026). Structural conservation and expanded functionality of hyper-stable human serum albumin variants. bioRxiv - the preprint server for biology. doi: 10.64898/2026.04.10.717531. Full text in Research Archive Show summary

  Abstract Human serum albumin (hSA) is the most abundant protein in human plasma, and its pharmacological properties, such as long plasma half-life mediated by the neonatal Fc receptor (FcRn) and its ability to bind endogenous and exogenous molecules, make it attractive for biotechnological applications. Currently, most wild type (WT) SAs are derived from human or bovine serum or produced in yeast and mammalian cells. Although well established, these methods are costly, difficult to reproduce, and not environmentally sustainable. Building on a previous study to design highly mutated hSA sequences, we extend the validation through an in-depth analysis of three engineered hSA variants; hSA1, hSA2, and hSA3, containing 16, 25, or 73 amino acid substitutions, respectively. These variants were designed for enhanced solubility, stability, and expression in Escherichia coli. All three variants showed low- micromolar affinities for hFcRn at pH 5.5, and negligible binding at pH 7.4. In a human endothelial cell-based recycling assay (HERA), the engineered hSA variants were recycled by hFcRn to the same extent as hSA isolated from serum. Exploring the properties of canonical drug-binding sites, warfarin affinity was comparable to WT hSA, whereas ibuprofen binding differed. Complementary cytotoxicity assays on human macrophages confirmed negligible toxicity and biocompatibility. A cryo-electron microscopy structure of hSA3 revealed that, despite extensive engineering, the native heart-shape of hSA, folding of domains, and its open conformation were preserved. These findings validate the structural integrity and functional adaptability of engineered hSA variants, underscoring their potential as versatile, animal-free solutions for next-generation therapeutics and biotechnological applications.

• Mukhamedova, Liya; Buchta, David; Trebichalská, Zuzana; Levdansky, Yevgen; Moravcová, Jana & Potěšil, David [Show all 14 contributors for this article] (2026). Particles of echovirus 18 open to release their genomes in vivo. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 123(30), p. 1–9. doi: 10.1073/pnas.2601182123. Full text in Research Archive
• Chernigovskaya, Maria; Quy, Khang Le; Stensland, Maria; Singh, Sachin; Nelson, Rowan & Yilmaz, Melih [Show all 19 contributors for this article] (2025). Systematic benchmarking of mass spectrometry-based antibody sequencing reveals methodological biases. Cell Systems. ISSN 2405-4712. 16(11). doi: 10.1016/j.cels.2025.101449. Full text in Research Archive Show summary

  The circulating antibody (Ab) repertoire is crucial for immune protection, holding significant immunological and biotechnological value. While bottom-up mass spectrometry (MS) is widely used for profiling the sequence diversity of circulating Abs (Ab repertoire sequencing [Ab-seq]), it has not been thoroughly benchmarked. We quantified the replicability and robustness of Ab-seq using six monoclonal Ab spike-ins in 70 combinations of concentration and oligoclonality, with and without polyclonal serum immunoglobulin G (IgG) background. Each combination underwent four protease treatments and was analyzed across four experimental and three technical replicates, totaling 3,360 liquid chromatography-tandem MS (LC-MS/MS) runs. We quantified the dependence of Ab-seq identification on Ab sequence, concentration, protease, presence of background IgGs, and bioinformatics methods. Integrating the data from experimental replicates, proteases, and bioinformatics tools enhanced Ab identification. De novo sequencing performed similarly to database-dependent methods at higher Ab concentrations, but de novo Ab reconstruction remains challenging. Our work provides a foundational resource for the field of MS-based Ab profiling. A record of this paper’s transparent peer review process is included in the supplemental information

• Aaen, Kristin Hovden; Testa, Maria Francesca; Nilsen, Jeannette; Tarantino, Rebecca; Canepari, Cesare & Benedusi, Mascia [Show all 16 contributors for this article] (2025). Tailored collagen binding of albumin-fused hyperactive coagulation factor IX dictates in vivo distribution and functional properties. Nature Communications. 16. doi: 10.1038/s41467-025-62955-9. Full text in Research Archive Show summary

  The efficacy of hemophilia B (HB) replacement therapy is evaluated by coagulation factor IX (FIX) activity in plasma, although FIX bound to extravascular type IV collagen (Col4) also contributes to efficient hemostasis. Here, we investigated the impact of engineering FIX for improved (K5R) or reduced (K5A) Col4 binding on the pharmacokinetic properties of FIX Padua, fused to human serum albumin (HSA QMP ) engineered for favorable neonatal Fc receptor (FcRn) engagement. Hyperactive features and extended plasma half-life in human FcRn expressing mice, attributed to FIX Padua and HSA QMP engineering, respectively, was confirmed. In HB mice, Padua KA -HSA QMP exhibited negligible extravascular distribution and the highest plasma levels at early time points followed by the steepest decay. Conversely, Padua KR -HSA QMP showed increased extravascular distribution and a 3-fold longer functional half-life (80 hours). These findings support the use of Padua KA -HSA QMP and Padua KR -HSA QMP as hyperactive short- or long-term therapeutics, respectively, with opportunities for tailored HB replacement therapy.

• Brennan, Frank R.; Polli, J. Ryan; Sathish, Jean; Ramones, Melissa; Wolf, Babette & Schlothauer, Tilman [Show all 30 contributors for this article] (2025). Impact of antibody Fc engineering on translational pharmacology, and safety: insights from industry case studies. mAbs. ISSN 1942-0862. 17(1). doi: 10.1080/19420862.2025.2505092. Full text in Research Archive Show summary

  Therapeutic monoclonal antibodies (mAbs) are often designed to not only bind targets via their antigen-binding domains (Fabs) but to also engage with cell surface receptors, FcγRs and FcRn, through their Fc regions, which may result in a variety of functional outcomes, including antibody- dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) and alteration of circulating half-lives. Engineering the Fc regions to achieve desirable pharmacology and pharmacokinetics is a widely adopted strategy in drug development. Fc regions can be modified through amino acid substitutions and glycoengineering, resulting in enhanced or reduced effector functions, preferential binding to FcR subtypes, or pH-dependent binding to FcRns. These alterations in binding and effector activities of mAbs may potentially also be accompanied by undesirable effects or safety concerns. Critical assessment of pharmacology and safety in the nonclinical setting is essential before exposing humans to the engineered mAb. For Fc-modified mAbs, the choice of in vitro and in vivo nonclinical pharmacology and safety models need to account for species differences in FcR expression and function, potentially divergent effects of Fc modifications in humans versus nonclinical species, impact of target and cognate ligand expression patterns, and potential impact of emergent anti-drug antibodies directed against the mAb. Using a variety of industry case studies, we highlight key aspects of nonclinical pharmacology and toxicology testing strategies, factors that influence choice of nonclinical models, translatability of findings, input from health authorities and suggest best practice approaches for nonclinical testing of Fc modified mAbs.

• Pilati, Diego; Agyei, Eugene Kusi; Elkhashab, Marwa; Fuchs, Elisabeth; Nielsen, Ian Helstrup & Bjerg, Tobias Wang [Show all 18 contributors for this article] (2025). Exploiting FcRn engagement of an albumin-CpG oligonucleotide covalent conjugate for potent TLR9 immune induction. Journal of Biological Chemistry. ISSN 0021-9258. 301(6). doi: 10.1016/j.jbc.2025.108508. Full text in Research Archive Show summary

  CpG-oligodeoxynucleotide (CpG ODN)-based Toll-like receptor (TLR) agonists are promising immunostimulatory adjuvants; however, low entry into TLR-rich cellular endosomal compartments and poor lymphatic accumulation limit clinical translation. In this work, we introduce a recombinant human serum albumin (rHA)-CpG ODN covalent conjugate (rHA-CpG) designed to exploit the neonatal Fc receptor (FcRn)-driven albumin cellular sorting pathway to maximize CpG delivery into TLR9-rich endosomes and accumulate in lymph nodes. Site-selective conjugation of CpG to albumin cysteine 34, distant from its main FcRn-binding interface, resulted in a retained pH-dependent human FcRn binding, and receptor-driven endosomal trafficking in a cellular recycling assay. Induction of tumor necrosis factor (TNF) secretion in THP-1 cells and interferon alpha (IFN-α) in human hematopoietic stem and progenitor cell (HSPC)-derived plasmacytoid dendritic cells (pDCs), in contrast, to a myeloid differentiation primary response 88 (MyD88) and TLR9 knockout cells, respectively, support TLR9-engagement. The rHA-CpG construct induced greater TNF-α than free CpG ODN in mouse RAW 264.7 cells, and in human peripheral blood mononuclear cells (PBMCs) and expansion of classical (CD14+CD16−) monocytes. Furthermore, greater accumulation of Cy5.5-labelled CpG in the inguinal (>3-fold) and axillary (>18-fold) lymph nodes was observed when conjugated to rHA compared to an unconjugated rHA/CpG mix following subcutaneous injection in mice. Moreover, increased LN accumulation of an rHA variant engineered with high FcRn-binding affinity supports an FcRn-driven mechanism. Demonstration of FcRn-mediated albumin targeting at intra- and extracellular sites provides the mechanistic basis for the potent immune induction observed using the novel rHA-CpG conjugate design class introduced in this work.

• Trabjerg, Esben; Nilsen, Jeannette; gjølberg, torleif; Andersen, Jan Terje; Leitner, Alexander & Rand, Kasper D. (2025). Identification of a direct interaction between the Fab domains of IgG antibodies and human FcRn upon IgG-FcRn complex formation. Communications Biology. 8(1). doi: 10.1038/s42003-025-08252-z. Full text in Research Archive Show summary

  IgGs have become successful drug scaffolds by combining specific target binding with the ability to induce cellular cytotoxicity. Furthermore, IgGs possess unusually long half-lives in the blood (2-3 weeks). IgGs achieve such extraordinary half-lives through a pH-dependent interaction with the FcRn-receptor whereby IgGs are recycled. No high-resolution structure of FcRn in complex with a full-length IgG is available, and the interaction was long thought to be mediated solely via the IgG-Fc. However, some IgGs with identical Fc-parts, but different Fab-domains, exhibit different half-lives, suggesting involvement of the Fab-domains in FcRn binding. Here, we employ structural mass spectrometry (HDX-MS and XL-MS) to explore the interaction of full-length IgGs with FcRn. HDX-MS and XL-MS experiments confirm an interaction between FcRn and the Fc-region of IgGs, through three cross-links between FcRn and the IgG-Fc-domain and a reduction in HDX in both the receptor and the Fc-region upon complex formation. However, FcRn-induced changes in HDX are also observed in the Fab-domains, supported by cross-links between the Fab-domains and the α3-domain of FcRn. Our results thus provide direct evidence for an IgG Fab-FcRn interaction. We envision that these results could advance the engineering of IgG-antibodies with tailored pharmacokinetics and enhanced efficacy.

• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Show all 32 contributors for this article] (2025). An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models. Nature Communications. 16(1), p. 1–16. doi: 10.1038/s41467-025-59353-6. Full text in Research Archive Show summary

  Although vaccines are usually given intramuscularly, the intranasal delivery route may lead to better mucosal protection and limit the spread of respiratory virus while easing administration and improving vaccine acceptance. The challenge, however, is to achieve delivery across the selective epithelial cell barrier. Here we report on a subunit vaccine platform, in which the antigen is genetically fused to albumin to facilitate FcRn-mediated transport across the mucosal barrier in the presence of adjuvant. Intranasal delivery in conventional and transgenic mouse models induces both systemic and mucosal antigen-specific antibody responses that protect against challenge with SARS-CoV-2 or influenza A. When benchmarked against an intramuscularly administered mRNA vaccine or an intranasally administered antigen fused to an alternative carrier of similar size, only the albumin-based intranasal vaccine yields robust mucosal IgA antibody responses. Our results thus suggest that this needle-free, albumin-based vaccine platform may be suited for vaccination against respiratory pathogens.

• Nilsen, Jeannette; Aaen, Kristin Hovden; Benjakul, Sopisa; Ruso-Julve, Fulgencio; Greiner, Thomas Uwe & Bejan, Daniela [Show all 11 contributors for this article] (2025). Enhanced plasma half-life and efficacy of engineered human albumin-fused GLP-1 despite enzymatic cleavage of its C-terminal end. Communications Biology. 8(1). doi: 10.1038/s42003-025-08249-8. Full text in Research Archive Show summary

  Albumin has a long plasma half-life due to engagement of the neonatal Fc receptor (FcRn), which prevents intracellular degradation. However, its C-terminal end can be cleaved by carboxypeptidase A, and removal of the last leucine residue (L585) weakens receptor binding, reducing its half-life from 20 days to 3.5 days in humans. This biology has so far been overlooked when designing human albumin-fused biologics. Thus, there is a need for an engineering strategy to secure favorable FcRn binding and pharmacokinetic properties. Here, we show that a branched aliphatic amino acid or methionine at position 585 of albumin is required for optimal receptor binding, which cannot be replaced to prevent enzymatic cleavage without negatively affecting FcRn engagement. As a solution, we report that C-terminally cleaved albumin can be efficiently rescued from intracellular degradation by introducing amino acid substitutions that improve FcRn binding. This albumin-engineering strategy was also effective when applied with a therapeutic fusion partner, glucagon-like peptide 1 (GLP-1), resulting in a 2-fold increase in plasma half-life and prolonged efficacy in human FcRn transgenic mice. We demonstrate how human albumin fusions should be tailored to ensure a long plasma half-life and enhanced efficacy of fused biologics, despite potential C-terminal cleavage in vivo.

• Gelli, Hitesh P.; Vazquez-Uribe, Ruben; Buckley, Stephen T.; Andersen, Jan Terje & Sommer, Morten Otto Alexander (2025). Advanced microbiome therapeutics for oral delivery of peptides and proteins: Advances, challenges, and opportunities. Advanced Drug Delivery Reviews. ISSN 0169-409X. 222. doi: 10.1016/j.addr.2025.115603. Full text in Research Archive Show summary

  Peptide and protein medicines have changed the therapeutic landscape for many diseases, yet oral delivery remains a significant challenge due to enzymatic degradation, instability, and poor permeability in the gastrointestinal tract. Advanced Microbiome Therapeutics (AMTs) could overcome some of these barriers by producing and releasing therapeutic peptides directly in the gastrointestinal tract. AMTs can localize peptide production at the site of absorption, providing either sustained or controlled release while potentially reducing side effects associated with systemic administration. Here, this review assesses the status of AMTs for oral peptide delivery and discusses the potential integration of permeation enhancers, mucoadhesive systems, and receptor-mediated transport strategies to improve oral bioavailability further. Combining these approaches could pave the way for more widespread oral delivery strategies for peptide and protein medicines.

• gjølberg, torleif; mester, simone; Calamera, Gaia; Telstad, Jenny Skjermo; Sandlie, Inger & Andersen, Jan Terje (2025). Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress. BioDrugs. ISSN 1173-8804. 39(3), p. 373–409. doi: 10.1007/s40259-025-00708-2. Full text in Research Archive Show summary

  Autoimmune diseases are highly prevalent and affect people at all ages, women more often than men. The most prominent immunological manifestation is the production of antibodies directed against self-antigens. In many cases, these antibodies (Abs) drive the pathogenesis by attacking the body’s own healthy cells, causing serious health problems that may be life threatening. Most autoantibodies are of the immunoglobulin G (IgG) isotype, which has a long plasma half-life and potent effector functions. Thus, there is a need for specific treatment options that rapidly eliminate these pathogenic IgG auto-Abs. In this review, we discuss how the neonatal Fc receptor (FcRn) acts as a regulator of the high levels of not only IgG Abs, but also albumin, by rescuing both these soluble proteins from cellular catabolism, and how a molecular and cellular understanding of this complex biology has spurred an intense interest in the development of FcRn-targeting strategies for the treatment of IgG-driven autoimmune diseases. We find that this emerging therapeutic class demonstrates efficacy within several autoimmune diseases with distinct pathophysiology. This offers hope for both new therapeutic avenues for highly prevalent diseases currently treated by other means, and rare diseases with no approved therapies to date. In addition, we elaborate on studies that have led to approval of the first FcRn antagonists, the clinical progress and structural design of molecules in the pipeline, their position in the overall therapeutic landscape of autoimmunity, the design of next-generation antagonists as well as the use of this receptor-targeting principle for other therapeutic applications.

• mester, simone; Chan, Chilam; Lustig, Marta; Foss, Stian; Jansen, J. H. Marco & Herigstad, Marie Leangen [Show all 17 contributors for this article] (2025). Engineering of anticancer human immunoglobulin A equipped with albumin for enhanced plasma half-life. PNAS Nexus. 4(2). doi: 10.1093/pnasnexus/pgaf042. Full text in Research Archive Show summary

  Most therapeutic antibodies are based on immunoglobulin G (IgG) due to their potent effector functions and long plasma half-life. However, also monomeric IgA has emerged as an attractive candidate for cancer treatment as, upon specific binding to tumor cells, it can activate myeloid cells, like polymorphonuclear leukocytes and macrophages, to kill the tumor cells by engaging the Fc α receptor I (FcαRI). Despite this favorable property, human IgA has a short plasma half-life in both mice and humans, which is clearly limiting preclinical studies in a translational perspective. Here, we report on albumin-equipped designs of human IgA antibodies that are long acting due to tailored binding to the human form of neonatal Fc receptor (FcRn), which is a natural plasma half-life regulator of albumin. Importantly, this was achieved without compromising the ability of IgA to engage and activate FcαRI-expressing effector cells for tumor cell killing in vitro and in vivo in a new mouse model transgenic for the human forms of FcRn and FcαRI. We further show that the potency of the engineered long-acting human IgA against tumor cells with intermediate target antigen expression levels could be enhanced by myeloid checkpoint inhibitors targeting the signal regulatory protein α-CD47 axis.

• Viermyr, Hans-Kittil; Halvorsen, Bente; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Barratt-Due, Andreas & Kåsine, Trine [Show all 73 contributors for this article] (2024). High viral loads combined with inflammatory markers predict disease severity in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial. Journal of Internal Medicine. ISSN 0954-6820. 296(3), p. 249–259. doi: 10.1111/joim.13820. Full text in Research Archive Show summary

  Objectives To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. Methods Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission). Results Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1β, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3–5, accompanied by IL-8 and IL-6 at days 7–10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline. Conclusions An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.

• Foss, Stian; Sakya, Siri Aastedatter; Aguinagalde, Leire; Lustig, Marta; Shaughnessy, Jutamas & Cruz, Ana Rita [Show all 25 contributors for this article] (2024). Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria. Nature Communications. 15(1). doi: 10.1038/s41467-024-46321-9. Full text in Research Archive Show summary

  Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions.

• Lustig, Marta; Hahn, Christoph; Herigstad, Marie Leangen; Andersen, Jan Terje; Leusen, Jeanette H. W. & Burger, Renate [Show all 7 contributors for this article] (2024). Sialylation inhibition improves macrophage mediated tumor cell phagocytosis of breast cancer cells triggered by therapeutic antibodies of different isotypes. Frontiers in Oncology. 14:1488668, p. 1–10. doi: 10.3389/fonc.2024.1488668. Full text in Research Archive Show summary

  Tumor cell phagocytosis by macrophages is considered a relevant mechanism of action for many therapeutic IgG antibodies. However, tumor cells employ several mechanisms to evade immune recognition, including hypersialylation. Here, we describe how reduction of sialic acid exposure on tumor cells promotes antibody-dependent tumor cell phagocytosis (ADCP) by macrophages. Incubation with the sialyltransferase inhibitor (STi) P-3Fax-Neu5Ac reduced sialylation on two breast cancer cell lines, rendering these cells more susceptible to macrophage mediated phagocytosis by EGFR or HER2 antibodies. This was observed with not only IgG1 and IgG2 antibodies but also IgA2 variants. These results show that inhibiting sialic acid exposure triggers enhanced tumor cell phagocytosis by macrophages irrespective of the antibody isotype and the tumor target antigen. Investigating the underlying mechanisms of enhanced ADCP, we observed reduced binding of soluble sialic acid-binding immunoglobulin-like lectins (Siglec)-7 and Siglec-9 to tumor cells after sialylation inhibition. However, Fc silent blocking antibodies against Siglec-7 or Siglec-9, or their combination, only marginally improved ADCP. Our results further promote the concept of cancer hypersialylation as immune escape mechanism, which could serve as target to improve tumor immunotherapy with monoclonal antibodies.

• Reusch, Johannes; Andersen, Jan Terje; Rant, Ulrich & Schlothauer, Tilman (2024). Insight into the avidity–affinity relationship of the bivalent, pH-dependent interaction between IgG and FcRn. mAbs. ISSN 1942-0862. 16:2361585(1), p. 1–17. doi: 10.1080/19420862.2024.2361585. Full text in Research Archive Show summary

  Monoclonal antibodies (mAbs) as therapeutics necessitate favorable pharmacokinetic properties, including extended serum half-life, achieved through pH-dependent binding to the neonatal Fc receptor (FcRn). While prior research has mainly investigated IgG-FcRn binding kinetics with a focus on single affinity values, it has been shown that each IgG molecule can engage two FcRn molecules throughout an endosomal pH gradient. As such, we present here a more comprehensive analysis of these interactions with an emphasis on both affinity and avidity by taking advantage of switchSENSE technology, a surface-based biosensor where recombinant FcRn was immobilized via short DNA nanolevers, mimicking the membranous orientation of the receptor. The results revealed insight into the avidity-to-affinity relationship, where assessing binding through a pH gradient ranging from pH 5.8 to 7.4 showed that the half-life extended IgG1-YTE has an affinity inflection point at pH 7.2, reflecting its engineering for improved FcRn binding compared with the wild-type counterpart. Furthermore, IgG1-YTE displayed a pH switch for the avidity enhancement factor at pH 6.2, reflecting strong receptor binding to both sides of the YTE-containing Fc, while avidity was abolished at pH 7.4. When compared with classical surface plasmon resonance (SPR) technology and complementary methods, the use of switchSENSE demonstrated superior capabilities in differentiating affinity from avidity within a single measurement. Thus, the methodology provides reliable kinetic rate parameters for both binding modes and their direct relationship as a function of pH. Also, it deciphers the potential effect of the variable Fab arms on FcRn binding, in which SPR has limitations. Our study offers guidance for how FcRn binding properties can be studied for IgG engineering strategies.

• Bashour, Habib; Smorodina, Eva; Pariset, Matteo; Zhong, Jahn; Akbar, Rahmad & Chernigovskaia, Maria [Show all 15 contributors for this article] (2024). Biophysical cartography of the native and human-engineered antibody landscapes quantifies the plasticity of antibody developability. Communications Biology. 7(1), p. 1–25. doi: 10.1038/s42003-024-06561-3. Full text in Research Archive Show summary

  Designing effective monoclonal antibody (mAb) therapeutics faces a multi-parameter optimization challenge known as “developability”, which reflects an antibody’s ability to progress through development stages based on its physicochemical properties. While natural antibodies may provide valuable guidance for mAb selection, we lack a comprehensive understanding of natural developability parameter (DP) plasticity (redundancy, predictability, sensitivity) and how the DP landscapes of human-engineered and natural antibodies relate to one another. These gaps hinder fundamental developability profile cartography. To chart natural and engineered DP landscapes, we computed 40 sequence- and 46 structure-based DPs of over two million native and human-engineered single-chain antibody sequences. We find lower redundancy among structure-based compared to sequence-based DPs. Sequence DP sensitivity to single amino acid substitutions varied by antibody region and DP, and structure DP values varied across the conformational ensemble of antibody structures. We show that sequence DPs are more predictable than structure-based ones across different machine-learning tasks and embeddings, indicating a constrained sequence-based design space. Human-engineered antibodies localize within the developability and sequence landscapes of natural antibodies, suggesting that human-engineered antibodies explore mere subspaces of the natural one. Our work quantifies the plasticity of antibody developability, providing a fundamental resource for multi-parameter therapeutic mAb design.

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• Andersen, Jan Terje (2026). Binding, Retention, or Recycling? Navigating FcRn Assays for PK Assessment. Full text in Research Archive
• Foss, Stian; Bay, Lilli Theres Eilertsen & Andersen, Jan Terje (2026). Design of antibodies for the treatment of Alzheimer's disease. doi: https:/civitan.no/2026/09/19/design-av-antistoffer-for-behandling-av-alzheimers-sykdom/. Full text in Research Archive
• Cyrusian, Sepehr & Andersen, Jan Terje (2026). Det usynlige forskningskuttet vi må snakke høyt om. doi: https:/www.khrono.no/det-usynlige-forskningskuttet-vi-ma-snakke-hoyt-om/1084625. Full text in Research Archive
• Bergseng, Anne & Andersen, Jan Terje (2026). Oda (35) fryktet for barnet: –⁠ En stor lettelse. doi: https:/www.vg.no/helse/i/GxXJzV/oda-35-fryktet-for-at-medisinen-kunne-paavirke-fosteret. Full text in Research Archive
• Kringstad, Kirsti; Nilsen, Jeannette & Andersen, Jan Terje (2026). Slik kan gravide bruke medisiner uten å skade babyen. doi: https:/www.nrk.no/trondelag/forskere-ved-oslo-universitetssykehus-med-ny-oppdagelse-og-graviditet-og-biologiske-medisiner-1.18001964. Full text in Research Archive
• Andersen, Jan Terje (2026). Cutting-Edge Cancer Research: From the Lab to the patient. Full text in Research Archive
• Andersen, Jan Terje & Nyquist-Andersen, Mari (2026). Laboratoriets dirigent. doi: https:/www.oslo-universitetssykehus.no/om-oss/innsikt/laboratoriets-dirigent/. Full text in Research Archive
• Andersen, Jan Terje (2026). Biologiske legemidler og virkningsmekanismer. Full text in Research Archive
• Kvaal, Julie Nybakk & Andersen, Jan Terje (2026). Ny oppdagelse kan gjøre biologiske legemidler tryggere for gravide. doi: https:/www.uio.no/forskning/forskningsnytt/artikler/2026/ny-oppdagelse-kan-gjore-biologiske-legemidler-tryggere-for-gravide.html. Full text in Research Archive
• Andersen, Jan Terje (2026). Albumin-Fused Antibodies May Reduce Fetal Exposure to Therapeutics. doi: https:/www.genengnews.com/topics/drug-discovery/albumin-fused-antibodies-may-reduce-fetal-exposure-to-therapeutics/. Full text in Research Archive
• Kvaal, Julie Nybakk & Andersen, Jan Terje (2026). Scientists uncover that albumin is prevented from crossing the placenta – open opportunities for design of long-acting biologic medicines with limited fetal exposure. doi: https:/www.eurekalert.org/news-releases/1139944. Full text in Research Archive
• Hagel, Sebastian Brauer; Storvik, Anne Grete & Andersen, Jan Terje (2026). OUS-forskningsgruppe inngår flerårig samarbeid med legemiddelselskap. doi: https:/medwatch.no/nyheter/legemidler_biotek/article19529670.ece?fbclid=IwY2xjawUeUGZwZG9mAWV4dG4DYWVtAjExAHNydGMGYXBwX2lkEDIyMjAzOTE3ODgyMDA4OTIAAR6Vy_6ioB3GiDvp9HrOJtAdRAavQ_CJtIU6qivdIwlRFk9UER8gYx-ms24BYQ_aem_1sos7bLlKq_c308m1zqn6Q. Full text in Research Archive
• Olweus, Johanna & Andersen, Jan Terje (2026). Debatt: Mange lovende teknologier stopper før de når pasienten. doi: https:/medwatch.no/nyheter/debatt/article19532426.ece. Full text in Research Archive
• Andersen, Jan Terje (2026). Politikken legger til rette — innovasjon skapes i samspill. doi: https:/www.khrono.no/politikken-legger-til-rette-innovasjon-skapes-i-samspill/1074018. Full text in Research Archive
• Hagel, Sebastian Brauer & Andersen, Jan Terje (2026). Jan Terje Andersen anerkjent av Novo Nordisk Fonden igjen. doi: https:/medwatch.no/nyheter/karriere_arbeidsliv/article19487339.ece. Full text in Research Archive
• Andersen, Jan Terje (2026). FRIPRO må styrkes — ikke begrenses. doi: https:/www.khrono.no/fripro-ma-styrkes-ikke-begrenses/1070726. Full text in Research Archive
• Andersen, Jan Terje (2026). Fra grunnforskning til innovasjon og næringslivssamarbeid. doi: https:/www.uio.no/forskning/scene-domus-bibliotheca/arrangementer/2026/morgendagens-teknologier. Full text in Research Archive
• Storvik, Anne Grete & Andersen, Jan Terje (2026). UiO får sentral rolle i EU-satsing på beredskap mot mpox og koppevirus. doi: https:/medwatch.no/nyheter/legemidler_biotek/article19344516.ece. Full text in Research Archive
• Andersen, Jan Terje (2026). Fra biologisk innsikt til medisinsk innovasjon. doi: https:/www.oslo-universitetssykehus.no/om-oss/innsikt/fra-biologisk-innsikt-til-medisinsk-innovasjon. Full text in Research Archive
• Andersen, Jan Terje (2026). The Brambell Receptor – From Biology to Versatile Therapeutic Applications. Full text in Research Archive
• Andersen, Jan Terje & Storvik, Anne Grete (2026). Norsk antistoffteknologi består første kliniske test og rigger for ny studie. doi: https:/medwatch.no/nyheter/legemidler_biotek/article19113710.ece. Full text in Research Archive
• Andersen, Jan Terje (2026). Fab-Fc Engineering for Enhanced Eradication of Bacteria and Cancer Cells. Full text in Research Archive
• Andersen, Jan Terje (2026). Fra dyptpløyende forskning til selskap og næringslivssamarbeid. Youtube. doi: https:/www.youtube.com/live/XLmIisterJw. Full text in Research Archive
• Andersen, Jan Terje (2026). Fremtidsrettet næringslivs­forskning: hva, hvor og når? doi: https:/www.khrono.no/fremtidsrettet-naeringslivsforskning-hva-hvor-og-nar/1031111. Full text in Research Archive
• Henmo, Ola; Andersen, Jan Terje & Dürkoop, Mirjam (2026). Professor propell gir medisiner superkrefter. [Internet]. Kreftforeningen.no. doi: https:/kreftforeningen.no/aktuelt/professor-propell-gir-medisiner-superkrefter/. Full text in Research Archive
• Andersen, Jan Terje (2026). Banebrytende grunnforskning åpner dører for samarbeid og selskaps­etableringer. doi: https:/www.khrono.no/banebrytende-grunnforskning-apner-dorer-for-samarbeid-og-selskapsetableringer/1026195. Full text in Research Archive
• Andersen, Jan Terje (2026). Antibody designs and effector function engineering for tailored outcome. Full text in Research Archive
• Benjakul, Sopisa & Andersen, Jan Terje (2026). FcRn – a bifunctional receptor with therapeutic applications. Full text in Research Archive
• Andersen, Jan Terje (2026). Banebrytende grunnforskning åpner dører for samarbeid og selskaps­etableringer. doi: https:/www.khrono.no/banebrytende-grunnforskning-apner-dorer-for-samarbeid-og-selskapsetableringer/1026195. Full text in Research Archive
• Andersen, Jan Terje (2026). Fremtidsrettet næringslivs­forskning: hva, hvor og når? doi: https:/www.khrono.no/fremtidsrettet-naeringslivsforskning-hva-hvor-og-nar/1031111. Full text in Research Archive
• Andersen, Jan Terje (2025). Developing respiratory vaccines that arrest viruses at the entrance. doi: https:/www.regjeringen.no/en/whats-new/challenges-and-opportunities-in-global-health/id3140979/?expand=factbox3141616. Full text in Research Archive
• Larsen, Atle Wester & Andersen, Jan Terje (2025). Får 8 millioner til kreftforskning: – Det forplikter! [Journal]. Halden Arbeiderblad. doi: https:/www.ha-halden.no/far-8-millioner-til-kreftforskning-det-forplikter/s/5-20-1816867. Full text in Research Archive
• Doeland, Elin Martine & Andersen, Jan Terje (2025). Ny teknologi kan forlenge virkningen av medisiner mot alvorlig blødersykdom. doi: https:/www.titan.uio.no/livsvitenskap/2025/vil-forlenge-virkningstiden-pa-medisiner-mot-alvor.html. Full text in Research Archive
• Hagel, Sebastian Brauer & Andersen, Jan Terje (2025). Andersen-gruppen klar med ny teknologi – jakter industripartner. doi: https:/medwatch.no/nyheter/legemidler_biotek/article18586679.ece. Full text in Research Archive
• Doeland, Elin Martine & Andersen, Jan Terje (2025). Vil forlenge virkningstiden på medisiner mot alvorlig blødersykdom. doi: https:/www.uio.no/forskning/forskningsnytt/artikler/2025/vil-forlenge-virkningstiden-pa-medisiner-mot-alvorlig-blodersykdom.html. Full text in Research Archive
• Andersen, Jan Terje (2025). Tailored collagen binding of albumin-fused hyperactive coagulation factor IX dictates in vivo distribution and functional properties. EurekAlert!. doi: https:/www.eurekalert.org/news-releases/1100134. Full text in Research Archive
• Andersen, Jan Terje & Doeland, Elin Martine (2025). Studie på mus: En slik vaksine kan trolig beskytte mot infeksjoner. doi: https:/www.forskning.no/dyreforsok-medisinske-metoder-partner/studie-pa-mus-en-slik-vaksine-kan-trolig-beskytte-mot-infeksjoner/2507244. Full text in Research Archive
• Andersen, Jan Terje (2025). Innovation Ambassador at Novo Nordisk Foundation: Distinguised Innovator Grant. doi: https:/www.youtube.com/watch?v=g-_kGnvhP7A&feature=youtu.be. Full text in Research Archive
• Andersen, Jan Terje & Doeland, Elin Martine (2025). Kan vi designe antistoffer som kan drepe kreftceller enda mer målrettet? doi: https:/www.med.uio.no/klinmed/om/aktuelt/aktuelle-saker/2025/kan-vi-designe-antistoffer-som-kan-drepe-kreftceller-enda-mer-malrettet.html. Full text in Research Archive
• Andersen, Jan Terje; Haslene-Hox, Hanne; Grødeland, Gunnveig; Cox, Rebecca Jane & Borgos, Sven Even F. (2025). Debatt: Norge bør utvikle og produsere vaksiner. USA er bare en av grunnene til det. doi: https:/www.dn.no/innlegg/vaksiner/medisin/teknologi/norge-bor-utvikle-og-produsere-vaksiner-usa-er-bare-en-av-grunnene-til-det/2-1-1792035. Full text in Research Archive
• Andersen, Jan Terje (2025). Innovasjonene står klare – hvorfor rigges det ikke bedre? doi: https:/medwatch.no/nyheter/debatt/article17976096.ece. Full text in Research Archive
• Andersen, Jan Terje (2025). Kronikk: Mer samarbeid med næringslivet? doi: https:/medwatch.no/nyheter/debatt/article18061515.ece. Full text in Research Archive
• Andersen, Jan Terje (2025). Debatt: Veikart for helsenæringen -fra festtaler til handling nå? doi: https:/medwatch.no/nyheter/debatt/article17949418.ece. Full text in Research Archive
• Andersen, Jan Terje & Doeland, Elin Martine (2025). En helt ny type vaksine kan trolig gi bedre beskyttelse mot infeksjoner. [Internet]. UiO. doi: https:/www.med.uio.no/klinmed/forskning/aktuelt/aktuelle-saker/2025/en-helt-ny-type-vaksine-kan-trolig-gi-bedre-beskyttelse-mot-infeksjoner.html#%3A%7E%3Atext=of%20this%20page-%2CEn%20helt%20ny%20type%20vaksine%20kan%20trolig%20gi%20bedre%20beskyttelse%2Cen%20ny%20studie%20p%C3%A5%20mus.. Full text in Research Archive
• Andersen, Jan Terje & Doeland, Elin Martine (2025). UiOs innovasjonspris til Jan Terje Andersen. [Internet]. UiO. doi: https:/www.med.uio.no/klinmed/om/aktuelt/aktuelle-saker/2025/uios-innovasjonspris-til-jan-terje-andersen.html. Full text in Research Archive
• Andersen, Jan Terje (2025). Kan antistoffer skreddersys til behandling av Alzheimer sykdom? doi: https:/civitan.no/2025/06/14/kan-antistoffer-skreddersys-til-behandling-av-alzheimers-sykdom/. Full text in Research Archive
• Andersen, Jan Terje & Storvik, Anne Grete (2025). Biotek-tungvekter starter nytt norsk selskap. [Internet]. MedWatch. doi: https:/medwatch.no/nyheter/legemidler_biotek/article18300024.ece. Full text in Research Archive
• Andersen, Jan Terje & Tidemann, Grethe (2025). UiOs priser 2025: Jeg vet hva som skal til for å lykkes. [Internet]. Uniforum. doi: https:/www.uniforum.uio.no/nyheter/2025/08/-jeg-er-sinnssykt-god-pa-samarbeid.html. Full text in Research Archive
• Andersen, Jan Terje & Dürkoop, Mirjam (2025). Fra biologi til medisinsk teknologi - Mirjam vil utgjøre en forskjell. [Internet]. OUS Innsikt. doi: https:/www.oslo-universitetssykehus.no/om-oss/innsikt/fra-biologi-til-medisinsk-teknologi---mirjam-vil-utgjore-en-forskjell/. Full text in Research Archive
• Andersen, Jan Terje; Anthi, Aina Karen & Kolderup, Anette (2025). Norsk studie med mulig vaksine-gjennom-brudd: –⁠ Nesten for godt til å være sant. [Journal]. Verdens Gang. Full text in Research Archive
• Andersen, Jan Terje (2025). Ny norsk vaksineteknologi mot luftveisinfeksjoner. [Internet]. MedWatch. Full text in Research Archive
• Andersen, Jan Terje; Anthi, Aina Karen & Kolderup, Anette (2025). An intranasal albumin-based vaccine technology for induction of protective mucosal and systemic antibody immunity against respiratory virus. EurekAlert!. Full text in Research Archive
• Andersen, Jan Terje & Foss, Stian (2025). Fra kreativ prisvinnende frisør til mastergrad i immunologi – nå skreddersyr han antistoffer. doi: https:/www.oslo-universitetssykehus.no/om-oss/ekspertsykehuset/fra-kreativ-prisvinnende-frisor-til-mastergrad-i-immunologi--na-skreddersyr-han-antistoffer/?fbclid=IwY2xjawNAlidleHRuA2FlbQIxMQABHvjZ2WE06Iq3x3UOwzURxwBvEPeJIWj6ywItxWEDVH-MoQuRsbH2vuAg6Wv8_aem_ngotdxM88AzjTLB24VBiqw. Full text in Research Archive
• Andersen, Jan Terje (2025). FcRn-guided engineering of tailored Antibody and Albumin based formats. Full text in Research Archive
• Andersen, Jan Terje (2025). Bridging groundbreaking research with research-driven innovation: The value of industrial collaboration. Full text in Research Archive
• Andersen, Jan Terje (2025). Biology-guided Engineering of Protein-based Technologies. Full text in Research Archive
• Olweus, Johanna & Andersen, Jan Terje (2025). Målrettet kreftbehandling. Proteiner og betydningen av fjorårets Nobelpris i kjemi. Full text in Research Archive
• Andersen, Jan Terje (2025). Biology-guided design of human albumin fusions – From cross-species binding differences to studies in transgenic mouse models. Full text in Research Archive
• Andersen, Jan Terje (2025). FcRn-Guided Engineering of Antibody and Albumin based Formats. Full text in Research Archive
• Andersen, Jan Terje (2025). Antibody designs and effector function engineering for tailored outcome. Full text in Research Archive
• Olweus, Johanna & Andersen, Jan Terje (2025). Målrettet kreftbehandling med KI. YouTube. doi: https:/www.bioteknologiradet.no/arrangement/bioteknologidagen-2025/. Full text in Research Archive
• Borgos, Sven Even F.; Haslene-Hox, Hanne; Grødeland, Gunnveig; Andersen, Jan Terje & Brokstad, Rebecca Jane Cox (2025). Norge bør utvikle og produsere vaksiner. USA er bare én av grunnene til det. Full text in Research Archive
• Borgos, Sven Even F.; Haslene-Hox, Hanne; Grødeland, Gunnveig; Andersen, Jan Terje; Brokstad, Rebecca Jane Cox & Tønseth, Svein (2025). Norge bør utvikle og produsere vaksiner. USA er bare én av grunnene til det. Full text in Research Archive Show summary

  https://www.dn.no/innlegg/vaksiner/medisin/teknologi/norge-bor-utvikle-og-produsere-vaksiner-usa-er-bare-en-av-grunnene-til-det/2-1-1792035

• Borgos, Sven Even F.; Brokstad, Rebecca Jane Cox; Grødeland, Gunnveig; Andersen, Jan Terje & Haslene-Hox, Hanne (2025). Norge bør utvikle og produsere vaksiner. USA er bare én av grunnene til det. Full text in Research Archive Show summary

  https://www.dn.no/innlegg/vaksiner/medisin/teknologi/norge-bor-utvikle-og-produsere-vaksiner-usa-er-bare-en-av-grunnene-til-det/2-1-1792035

• Brækhus, Leni Aurora; Grødeland, Gunnveig & Andersen, Jan Terje (2025). Grødeland og Andersen hedret som fremragende UiO-ansatte. [Journal]. Dagens Medisin. Full text in Research Archive
• Kvaal, Julie Nybakk & Andersen, Jan Terje (2024). I fremtiden trenger du kanskje ikke ta faste medisiner like ofte som i dag. [Internet]. Forskning.no. doi: https:/www.forskning.no/bioteknologi-medisiner-partner/i-fremtiden-trenger-du-kanskje-ikke-ta-faste-medisiner-like-ofte-som-i-dag/2344879. Full text in Research Archive
• Andersen, Jan Terje; Kvaal, Julie Nybakk & Foss, Stian (2024). Vil gi medisiner superkrefter med unik teknologi. [Internet]. UiO hjemmeside. doi: https:/www.med.uio.no/klinmed/forskning/aktuelt/aktuelle-saker/2024/vil-gi-medisiner-superkrefter-med-unik-teknologi.html. Full text in Research Archive
• Andersen, Jan Terje & Omvik, Eirik (2024). Authera-gründer har tatt patent på ny antistoffteknologi. [Internet]. Medwatch. doi: https:/medwatch.no/nyheter/legemidler_biotek/article16905971.ece. Full text in Research Archive
• Omvik, Eirik & Andersen, Jan Terje (2024). Har startet fase 1-studie med norskutviklet antistoffteknologi. [Internet]. Medwatch. doi: https:/medwatch.no/nyheter/legemidler_biotek/article17053235.ece. Full text in Research Archive
• Berg, Trond & Andersen, Jan Terje (2024). Licensing validates Norwegian platform technology for the development of tailored monoclonal antibodies. [Internet]. Oslo Universitetssykehus hjemmeside. doi: https:/www.ous-research.no/no/ous/news/24199. Full text in Research Archive
• Treider, Hans Petter & Andersen, Jan Terje (2024). Ny medisin kan revolusjonere behandling av alvorlige sykdommer - Jan Terje skaper medisiner med superkrefter. [Journal]. Verdens Gang. doi: https:/www.vg.no/helse/i/Rz95VJ/ny-medisin-kan-revolusjonere-behandlingen-av-alvorlige-sykdommer. Full text in Research Archive
• Andersen, Jan Terje (2024). Dive into the advancements in FcRn. Full text in Research Archive
• Andersen, Jan Terje (2024). A versatile antibody technology allowing design of long-acting antibodies with tailored target-dependent mode of actions. EurekAlert!. doi: https:/www.eurekalert.org/news-releases/1036880. Full text in Research Archive
• Andersen, Jan Terje (2024). Biology-guided Engineering of Versatile Antibody and Albumin Technologies. Full text in Research Archive
• Andersen, Jan Terje (2024). Co-chair of the Keynote Session, Antibody Engineering & Therapeutics Europe 2024, London, UK. Full text in Research Archive
• Kristensen, Hanne Mette Dyrlie & Andersen, Jan Terje (2024). Immunology – a Pillar in Norway’s Life Science Innovation. TLSC News. doi: https:/nordiclifescience.org/immunology-a-pillar-in-norways-life-science-innovation/. Full text in Research Archive
• Andersen, Jan Terje (2024). Nordic Life Science: Column: The amazing structures of proteins. [Internet]. Nordic Life Science: Column. doi: https:/nordiclifescience.org/featured-article/the-amazing-structures-of-proteins/. Full text in Research Archive
• Andersen, Jan Terje & Kristensen, Hanne Mette Dyrlie (2024). Protein, protien, protein! doi: https:/nordiclifescience.org/protein-protein-protein/. Full text in Research Archive
• Ruso-Julve, Fulgencio; Sakya, Siri Aastedatter; Kolderup, Anette; Tjärnhage, Elias; Benjakul, Sopisa & Nilsen, Jeannette [Show all 10 contributors for this article] (2024). Engineered albumin as an effector negative scaffold for tailored design of long acting antibody fragment fusions. European Journal of Immunology. ISSN 0014-2980. 54, p. 802–802. Full text in Research Archive
• Ruso-Julve, Fulgencio; Sakya, Siri A; Kolderup, Heidi Anette; Tjärnhage, Elias; Benjakul, Sopisa & Nilsen, Jeannette [Show all 10 contributors for this article] (2024). Engineered human albumin as an effector negative scaffold for tailored design of long-acting antibody fragment fusions. Full text in Research Archive
• Andersen, Jan Terje; mester, simone & gjølberg, torleif (2024). Slik skjøt oppstartsraketten Authera fart. [Internet]. Medwatch.no. Full text in Research Archive
• Andersen, Jan Terje (2024). Har startet fase 1 studie med norskutviklet antistoffteknologi. [Internet]. Medwatch.no. Full text in Research Archive

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