Retinitis pigmentosa (RP) affects 1 in 3,000 individuals worldwide, with 30%-40% of cases inherited as autosomal dominant (AD). Mutations in RHO (RP4) are the most common cause of ADRP. Because most RHO mutations exert gain-of-function or dominant-negative effects, conventional gene supplementation is insufficient, requiring mutant allele inactivation. Allele-specific editing is impractical, as each mutation requires a unique therapeutic strategy. We present a mutation-agnostic, RHO-specific approach using adeno-associated viral vector-mediated homology-independent targeted integration (AAV-HITI). Optimized donor DNA design enables targeted integration and efficient transgene expression from the endogenous RHO locus. In a humanized RP4 mouse model harboring the RHO P23H mutant allele alongside an endogenous wild-type mouse Rho allele, AAV-HITI significantly improves retinal structure, function, and visual acuity up to 1 year post-treatment. Comprehensive molecular analyses characterize on-target editing in mouse retina and off-target editing in a human cell line. These findings establish an effective, human-centric AAV-HITI platform for RP4 and support its evaluation in this and other dominant genetic conditions.
F. Esposito, Arjun Padmanabhan, M. Rhiel et al.· Cell Reports Medicine· 0 citations
Adoptive immunotherapies have emerged as a promising strategy in the treatment of hematological malignancies. To date, seven chimeric antigen receptor (CAR)-T cell products have obtained market authorization in Europe for B-cell malignancies, where they have revolutionized treatment for eligible patients. In addition, natural killer (NK) cells and γδ T cells are of particular interest for cell-based therapies due to their strong intrinsic cytotoxicity and favorable safety profile. Addressing challenges facing the clinical translation of NK cell therapies was one of the issues discussed in the NK & ILC Symposium that took place in Freiburg, Germany from March 11 to 13, 2026, as the annual meeting of the NK & ILC study group of the German Society for Immunology (DGfI). Topics ranging from basic immunological research to technological innovations and clinical trial results were discussed during the 3-day conference, spanning over 40 presentations and 100 posters. A highlight of the conference was a workshop featuring short presentations and a panel discussion that focused specifically on the current challenges and future prospects of the clinical implementation of NK cell therapies; the findings of this workshop are summarized in this opinion paper. Graphical abstract
L. Knapp, Katharina Sophie Fischer, Janika Sosat et al.· Human Gene Therapy· 0 citations
The results suggest that this approach may overcome the reliance on busulfan or other myeloablative conditioning regimens with their associated morbidities, and by enabling toxin-free conditioning and in vivo selection of edited cells, may facilitate clinical implementation of these highly valuable genetic therapies.
Romina Marone, Rosalba Lepore, K. Paschoudi et al.· bioRxiv· 0 citations
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