Abstract：
:Systemic gene delivery into muscle has been a major challenge for muscular dystrophy gene therapy, with capillary blood vessels posing the principle barrier and limiting vector dissemination. Previous efforts to deliver genes into multiple muscles have relied on isolated vessel perfusion or pharmacological interventions to enforce broad vector distribution. We compared the efficiency of multiple adeno-associated virus (AAV) vectors after a single injection via intraperitoneal or intravenous routes without additional intervention. We show that AAV8 is the most efficient vector for crossing the blood vessel barrier to attain systemic gene transfer in both skeletal and cardiac muscles of mice and hamsters. Serotypes such as AAV1 and AAV6, which demonstrate robust infection in skeletal muscle cells, were less effective in crossing the blood vessel barrier. Gene expression persisted in muscle and heart, but diminished in tissues undergoing rapid cell division, such as neonatal liver. This technology should prove useful for muscle-directed systemic gene therapy.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Wang Z,Zhu T,Qiao C,Zhou L,Wang B,Zhang J,Chen C,Li J,Xiao Xdoi
10.1038/nbt1073subject
Has Abstractpub_date
2005-03-01 00:00:00pages
321-8issue
3eissn
1087-0156issn
1546-1696pii
nbt1073journal_volume
23pub_type
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