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Selective uptake and sustained expression of AAV vectors following subcutaneous delivery
Author(s) -
Donahue Brian A.,
McArthur James G.,
Spratt S. Kaye,
Bohl Delphine,
Lagarde Catherine,
Sanchez Lisa,
Kaspar Brian A.,
Sloan Barbara A.,
Lee Ya Li,
Danos Olivier,
Snyder Richard O.
Publication year - 1999
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/(sici)1521-2254(199901/02)1:1<31::aid-jgm3>3.0.co;2-t
Subject(s) - expression (computer science) , microbiology and biotechnology , chemistry , medicine , biology , computer science , programming language
Background Recombinant adeno‐associated viral (rAAV) vectors are capable of long‐term expression of secreted and intracellular proteins following delivery to muscle, liver, and the central nervous system. In this study, we have evaluated subcutaneous injection of rAAV encoding a variety of transgenes as an alternative route of administration for the systemic delivery of therapeutic proteins. Methods rAAV vectors encoding the human factor IX, human interferon‐ α 2a, murine erythropoietin (epo), and Escherichia coli lacZ genes were used for subcutaneous delivery into mature immunocompetent mice. Expression of factor IX and interferon in mouse serum was measured by ELISA. Expression of Epo was monitored by an increase in hemotocrit and by RIA. The tissue tropism of AAV transduction was determined by histochemistry following administration of the lacZ vector. Results Long‐term protein expression (at least one year) is demonstrated in the serum of immunocompetent mice following subcutaneous delivery of AAV vectors encoding the human factor IX and interferon genes. The murine epo gene delivered via this route resulted in levels of Epo that correlate with increased hematocrits of up to 90% for a duration of nine months. rAAV encoding the lacZ gene revealed that the panniculus carnosus, a skeletal muscle layer of the skin, was transduced upon subcutaneous administration.Conclusions This study shows that long‐term expression of secreted proteins can be achieved using rAAV vectors injected subcutaneously as a single administration. The observation that the panniculus carnosus is the primary tissue transduced by rAAV illustrates the high tropism of rAAV for skeletal muscle. Copyright © 1999 John Wiley & Sons, Ltd.