Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and expression of transduced sequences in mice

• Published in: Gene Vol. 190; no. 1; pp. 203 - 210
• Main Authors: Ponnazhagan, Selvarangan, Mukherjee, Pinku, Yoder, Mervin C., Wang, Xu-Shan, Zhou, Shang Zhen, Kaplan, Johanne, Wadsworth, Samuel, Srivastava, Arun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 29.04.1997
• Subjects: adeno-associated virus 2; Animals; Bone marrow transplantation; Dependovirus - genetics; Gene delivery; Gene therapy; Gene Transfer Techniques; Genetic Vectors; Hematopoiesis; Hematopoietic Stem Cells - metabolism; Liver - metabolism; Mice; Mice, Inbred C57BL; Recombinant DNA; Recombination, Genetic; Transduction, Genetic; Tropism; Viral vectors; ITR; moi; Bone marrow transplantation; Viral vectors; CFU-S; p.i; Recombinant DNA; FACS; CMV; bp; βGal; i.v; Gene delivery; HS-2; re; XGal; Hematopoiesis; AAV; FBS; CTL; LCR; Gene therapy; wt; PCR
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/S0378-1119(96)00576-8

Adeno-associated virus 2 (AAV), a non-pathogenic human parvovirus, is gaining attention as a vector for its potential use in human gene therapy. However, few studies have examined the safety and the efficacy of this vector system in vivo. We report here that recombinant AAV vectors, when directly injected intravenously in mice, accumulated predominantly in liver cells, suggesting that AAV may possess in vivo organ-tropism for liver. The transduced lacZ reporter gene was expressed in hepatocytes in the liver and, at the level examined, did not appear to induce any detectable cytotoxic T lymphocyte response against βGal. AAV-mediated transduction of murine hematopoietic progenitor cells ex vivo followed by transplantation into lethally irradiated syngeneic mice also revealed high-efficiency gene transfer into progeny cells without any observable cytotoxicity or deleterious effect. The transduced reporter gene sequences were also expressed in mice in vivo. The AAV-based vectors may thus prove useful as a potentially safe alternative to the more commonly used retrovirus- and adenovirus-based vector systems.