Autoimmunity and Gene Therapy: The nemesis of autoimmunity

Giannoukakis, Nick; Trucco, Massimo

doi:10.1038/sj.gt.3302187

Cited by 1 publication

(2 citation statements)

References 11 publications

(11 reference statements)

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“…The use of serotypes 6 and 8 may also help to avoid the deleterious effects of the immune reaction against AAV-delivered transgene products found particularly strong in autoimmunity susceptible strains of Transduction of pancreatic islets with double-stranded AAV KK Rehman et al mice. 36,37 However, the efficiency of transduction that we have observed with dsAAV serotype 2 already should be sufficient for many therapeutic applications.…”

Section: 34mentioning

confidence: 99%

“…The pseodotyped AAV packaging plasmids, however, contained each individual serotype capsid gene and coupled with an uniform AAV2 rep gene. [30][31][32][33][34][35][36][37][38][39][40][41] The resulting AAV serotype viral particles containing the identical AAV vector DNA cassette of GFP gene, packaged by specific serotype capsids for AAV1, AAV2, AAV5, AAV6, AAV7, and AAV8. The different AAV viruses were purified twice with CsCl gradient ultracentrifugation 42 and the titers of vector-genome (vg) particles were determined by a standard dot-blot assay.…”

Section: Construction and Production Of Aav Vectormentioning

confidence: 99%

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Efficient gene delivery to human and rodent islets with double-stranded (ds) AAV-based vectors

et al. 2005

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Transplantation of allogeneic pancreatic islets is an effective approach to treat type 1 diabetes. To bypass the need for systemic administration of immunosuppression drugs following transplantation, approaches to genetically modify allogeneic islets to express anti-inflammatory, immunosuppressive, or antiapoptotic proteins prior to transplantation are being developed. Adeno-associated viral (AAV) based vectors have been used for gene transfer to islets, but the efficiency of functional transduction is low. Recently, doublestranded (ds) or double-copy (dc) based AAV vectors have been developed that allow for more rapid and efficient AAVmediated transgene expression following transduction. Here we demonstrate that intact human and murine islets can be transduced with dsAAV2-eGFP efficiently compared to single-stranded AAV2-eGFP. Furthermore, our results demonstrate that murine islets transduced with dsAAV2-eGFP have normal islet glucose responsiveness, viability, and islet insulin content. Transplantation of the dsAAV2-eGFP transduced islet restored normal glycemia in diabetic mice without eliciting an immune response. Significant dsAAV2-mediated eGFP expression was observed in the islet grafts for at least 6 months post-transplant. Finally, we demonstrated that dsAAV serotypes 2, 6, and 8 infect human islets efficiently. Taken together, these results suggest that dsAAV based vectors are highly appropriate for gene transfer to islets to facilitate transplantation.

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Section: 34mentioning

confidence: 99%