Improved Adeno-associated Virus (AAV) Serotype 1 and 5 Vectors for Gene Therapy

Overview

Journal Sci Rep

Specialty Science

Date 2013 May 14

PMID 23665951

Citations 28

Authors

Dwaipayan Sen

Balaji Balakrishnan

Nishanth Gabriel

Prachi Agrawal

Vaani Roshini

Rekha Samuel

Alok Srivastava

Giridhara R Jayandharan

Affiliations

Soon will be listed here.

Abstract

Despite significant advancements with recombinant AAV2 or AAV8 vectors for liver directed gene therapy in humans, it is well-recognized that host and vector-related immune challenges need to be overcome for long-term gene transfer. To overcome these limitations, alternate AAV serotypes (1-10) are being rigorously evaluated. AAV5 is the most divergent (55% similarity vs. other serotypes) and like AAV1 vector is known to transduce liver efficiently. AAV1 and AAV5 vectors are also immunologically distinct by virtue of their low seroprevalence and minimal cross reactivity against pre-existing AAV2 neutralizing antibodies. Here, we demonstrate that targeted bio-engineering of these vectors, augment their gene expression in murine hepatocytes in vivo (up to 16-fold). These studies demonstrate the feasibility of the use of these novel AAV1 and AAV5 vectors for potential gene therapy of diseases like hemophilia.

Citing Articles

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Evaluating Gene Therapy as a Potential Paradigm Shift in Treating Severe Hemophilia.

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