Factor IX Expression in Skeletal Muscle of a Severe Hemophilia B Patient 10 Years After AAV-mediated Gene Transfer

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2012 Jan 25

PMID 22271447

Citations 117

Authors

George Buchlis

Gregory M Podsakoff

Antonetta Radu

Sarah M Hawk

Alan W Flake

Federico Mingozzi

Katherine A High

Affiliations

Soon will be listed here.

Abstract

In previous work we transferred a human factor IX-encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier who died of causes unrelated to gene transfer. Using Western blot, IHC, and immunofluorescent staining, we show persistent factor IX expression in injected muscle tissue. F.IX transcripts were detected in injected skeletal muscle using RT-PCR, and isolated whole genomic DNA tested positive for the presence of the transferred AAV vector sequence. This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer.

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