986. Efficient Gene Delivery to Human and Rodent Islets with Double Stranded (ds)-AAV2-Based Vectors

Abstract

Top of pageAbstract Islet transplantation represents a potential cure for Type 1 diabetes mellitus. However, the survival of allogeneic islets following transplant, especially in an autoimmune background is extremely poor. The transfer of immunomodulatory and anti-apoptotic genes into islet cells can improve islet function and survival post-transplant. Several different viral vectors have been used to infect intact rodent and human islets. The immunogenecity, and transient gene expression of adenoviral vectors and the high multiplicity of infection of adeno-associated viral vectors required for infection have limited their use in clinical human islet transplantation. We have compared the ability of ds-AAV2 and ss-AAV2 viral vectors to transfer green fluorescent protein gene into intact human and murine islets. We demonstrate that ds-AAV-2 efficiently transduced both human and murine islets at lower MOI as compared to ss-AAV without impairing islet viability and insulin secretion capacity of b-cells both in vitro and in vivo following transplantation. Moreover, islets transduced with dsAAV express GFP up to six months in syngeneic islet grafts without eliciting immune response. In conclusion, these results demonstrate dsAAV viral vectors are non-toxic, transduce islet cells efficiently and can be used as tool to deliver therapeutic genes in to islet cells to facilitate future clinical islet transplantation.