Oline Eriksen Rio

• Labun, Kornel; Rio, Oline Eriksen; Dahal-Koirala, Shiva; Komisarczuk, Anna Zofia; Valen, Eivind & Haapaniemi, Emma Maria (2026). SNIPSNP: precision design of CRISPR/Cas9 knock-in reagents for variant correction and disease modeling. Nucleic Acids Research (NAR). ISSN 0305-1048. 54(W1), s. W145–W153. doi: 10.1093/nar/gkag409. Fulltekst i vitenarkiv Vis sammendrag

  We present SNIPSNP (crisprtools.org/snipsnp), a comprehensive bioinformatics pipeline for designing experiments for CRISPR-induced homology-directed repair (HDR). The tool addresses the critical challenge of Cas9 re-cleavage by simplifying the selection of “blocking” silent variants that are effective at inhibiting RNP binding upon donor-templated editing. SNIPSNP handles complex edits, including indels, and uses multi-objective optimization to balance editing efficiency with biological safety. From user-defined wild-type and desired HDR alleles, the pipeline identifies candidate guides, annotating them with integrated efficiency scores and genome-wide off-target assessments. Uniquely, SNIPSNP evaluates guide binding against the post-edit genome to determine whether the therapeutic variant alone disrupts repeated Cas9 recognition. When necessary, it introduces synonymous blocking variants, prioritizing PAM and seed regions to minimize re-cleavage probability and editing of the wild-type (WT) allele when editing heterozygous variants. All candidate modifications undergo safety profiling and prioritization of known benign variants from dbSNP. We experimentally validated SNIPSNP and benchmarked it on pathogenic inborn error of immunity variants in primary patient T-cells. Across loci, SNIPSNP-designed templates outperform standard “correction-only” strategies, demonstrating enhanced precision editing, and reduced re-cleavage, establishing SNIPSNP as a robust platform for genome editing and disease modeling.

• Labun, Kornel; Rio, Oline Eriksen; Tjeldnes, Håkon; Swirski, Michał; Komisarczuk, Anna Zofia & Haapaniemi, Emma Maria [Vis alle 7 forfattere av denne artikkelen] (2025). CHOPOFF: symbolic alignments enable fast and sensitive CRISPR off-target detection. bioRxiv - the preprint server for biology. doi: 10.1101/2025.01.06.603201. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT CRISPR/Cas systems offer powerful tools for genome editing, but their therapeutic application is hampered by the risk of unintended off-target mutations. Many molecular methods have been established to detect off-target editing, however, their sensitivity depends on first identifying potential sites using in silico methods. However, these in silico prediction methods are challenged by a trade-off between speed and sensitivity, and can fail to comprehensively detect all edited off-target sites. Here, we demonstrate that ignoring bulges has led to missing editing at off-target sites in previous studies and that continuing this practice can lead to inflated claims of fidelity. As a solution, we introduce the concept of symbolic alignments to efficiently identify off-targets without sacrificing sensitivity. We further present specialized data structures that enable rapid, alignment-free probabilistic ranking of guide RNAs based on their predicted off-target burden. Implemented in the tool CHOPOFF, these innovations accommodate mismatches, bulges (insertions/deletions), and incorporate genomic sequence variants for personalized off-target assessment. Benchmarking demonstrates that CHOPOFF significantly outperforms state-of-the-art tools in both prediction accuracy and computational speed. Availability CHOPOFF command line available at https://github.com/JokingHero/CHOPOFF.jl CHOPOFF web server available at https://crisprtools.org/chopoff

• Moen, Christian Arvei; Falkenthal, Thea Eline Hetland; Torkelsen, Tor Kristian; Hopland, Anders Mølster; Rio, Oline Eriksen & Honore, Alfred [Vis alle 17 forfattere av denne artikkelen] (2023). Penile Cancers Attributed to Human Papillomavirus Are Associated with Improved Survival for Node-positive Patients. Findings from a Norwegian Cohort Study Spanning 50 Years. European Urology Oncology (EUO). 7(4), s. 778–785. doi: 10.1016/j.euo.2023.10.013. Fulltekst i vitenarkiv Vis sammendrag

  Background: Human papillomavirus (HPV) infection is a risk factor for the development of penile squamous cell carcinoma (PSCC). It remains inconclusive whether HPV-related PSCC has a different prognosis from non-HPV-related PSCC. Objective: To investigate the relationship between HPV status and survival as well as temporal changes in the proportion of HPV-related PSCC. Design, setting, and participants: A retrospective cohort of 277 patients treated in Norway between 1973 and 2022 was investigated for HPV DNA in tumor tissue. Clinicopathological variables and disease course were registered. Outcome measurements and statistical analysis: Kaplan-Meier curves and Cox regression were used to investigate the determinants of cancer-specific survival (CSS). The chi-square test for trend in proportions enabled investigation of temporal changes in the HPV-related proportion of PSCC patients treated in Western Norway (n = 211). Results and limitations: HPV DNA was detected in tumor tissue from 131 (47%) patients. Stratified by HPV status, 5-yr CSS did not differ between groups (p = 0.37). When investigating only node-positive patients, however, presence of HPV DNA was an independent predictor of better survival in multivariable Cox regression after adjustment for age, nodal stage, and adjuvant therapy (hazard ratio 0.54, 95% confidence interval: [0.30-0.99], p = 0.04). In cases from Western Norway, an increasing proportion of HPV-related cases over time was found (p = 0.01). The main limitation is the retrospective study design. Conclusions: HPV DNA in tumor tissue was associated with significantly better CSS for node-positive patients. The proportion of HPV DNA-positive PSCC has increased significantly in Western Norway over the past 50 yr. Patient summary: We investigated the impact of human papillomavirus (HPV) on the survival of penile cancer patients treated over a 50-yr period in Norway. We found that for patients with lymph node metastasis, survival was better for HPV-related cases. We also found that the proportion of cases due to HPV has increased in Western Norway. Keywords: Cancer-specific survival; Human papillomavirus; Net survival; Penile cancer; Penile squamous cell carcinoma.

Se alle arbeider i NVA

• Rio, Oline Eriksen; Labun, Kornel; Dahal-Koirala, Shiva; Komisarczuk, Anna Zofia; Valen, Eivind & Haapaniemi, Emma Maria (2026). SNIPSNP: precision design of CRISPR reagents. Fulltekst i vitenarkiv
• Haugen, Frida Loe; Mamia, Katariina Aino Inkeri; Rio, Oline Eriksen; Sollano, Anniken Solveig Matheson; Li, Zhuokun & Labun, Kornel [Vis alle 20 forfattere av denne artikkelen] (2025). CRISPR/Cas9-based pipeline to introduce custom edits in autologous T cells. Fulltekst i vitenarkiv
• Haugen, Frida Loe; Mamia, Katariina Aino Inkeri; Rio, Oline Eriksen; Sollano, Anniken Solveig Matheson; Li, Zhuokun & Labun, Kornel [Vis alle 20 forfattere av denne artikkelen] (2025). CRISPR-Cas9 pipeline for custom editing in autologous T cells. doi: https:/event.fourwaves.com/crisprmed25/abstracts/b5911e8e-de8e-4ee4-b8e2-9f08cc2f31d8. Fulltekst i vitenarkiv Vis sammendrag

  CRISPR/Cas9 gene editing technology is a promising tool for correcting pathogenic variants in Inborn Errors of Immunity (IEIs). Current IEI correction strategies rely on cDNA knock-in or gene knockout, which can disrupt gene expression and need extensive optimization. To address this, we developed a safe, efficient CRISPR/Cas9-based T cell editing pipeline using HDR for SNV correction. We observe a rapid and selective expansion of CD3+ T cells from patient peripheral blood following an 8-day cytokine stimulation. To enhance HDR outcomes, we explored multiple strategies and developed an optimized T cell pipeline capable of achieving up to 80% HDR. We found no pre-malignant off-target effects or karyotypic, transcriptomic, or proteomic abnormalities in patient T cells analysed with GUIDE-seq, scRNA-seq, long-read WGS, and proteomics. We observed functional correction of the disease phenotype in patient T cells demonstrated on transcriptomic level by single cell RNA sequencing, on proteomic level by Mass Spectrometry and in cell culture-based assays. So far, we have implemented the pipeline and corrected 12 unique SNV mutations causing 8 diverse IEIs. This platform is designed to streamline CRISPR tool discovery/optimization and can be further developed into a GMP-compatible, scaled-up process for salvage therapy in T cell-related IEIs.

• Rio, Oline Eriksen (2024). CRISPR corrected T-cells for personalized therapy of IEIs. Fulltekst i vitenarkiv
• Haapaniemi, Emma Maria; Dahal-Koirala, Shiva; Komisarczuk, Anna Zofia; Mamia, Katariina Aino Inkeri; Rio, Oline Eriksen & Haugen, Frida Høsøien [Vis alle 10 forfattere av denne artikkelen] (2024). Presentation of precision pediatrics and gene editing group. Fulltekst i vitenarkiv
• Rio, Oline Eriksen; Komisarczuk, Anna Zofia; Labun, Kornel & Haapaniemi, Emma Maria (2023). CRISPR-Cas9 corrected T cells for personalized primary immunodeficiency disease (PIDD) therapy. Fulltekst i vitenarkiv
• Rio, Oline Eriksen; Komisarczuk, Anna Zofia; Labun, Kornel & Haapaniemi, Emma Maria (2023). CRISPR-Cas9 corrected T cells for personalized primary immunodeficiency disease (PIDD) therapy. Fulltekst i vitenarkiv
• Rio, Oline Eriksen; Haapaniemi, Emma Maria; Komisarczuk, Anna Zofia & Labun, Kornel (2023). CRISPR-Cas9 corrected T cells for personalized primary immunodeficiency disease (PIDD) therapy. Fulltekst i vitenarkiv

Se alle arbeider i NVA