Journal
BLOOD
Volume 119, Issue 13, Pages 3038-3041Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-09-382317
Keywords
-
Categories
Funding
- National Institutes of Health [HL64190, T32-HL07439]
- Howard Hughes Medical Institute
- Center for Cellular and Molecular Therapeutics at Children's Hospital of Philadelphia
Ask authors/readers for more resources
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. (Blood. 2012;119(13):3038-3041)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available