Intravenous injection of a foamy virus vector to correct canine SCID-X1.

Publication Type:

Journal Article

Source:

Blood, Volume 123, Issue 23, p.3578-84 (2014)

Keywords:

2014, April 2014, Center-Authored Paper, Clinical Research Division, Flow Cytometry Core Facility, Genomics Core Facility, Shared Resources

Abstract:

Current approaches to hematopoietic stem cell (HSC) gene therapy involve the collection and ex vivo manipulation of HSCs, a process associated with loss of stem cell multipotency and engraftment potential. An alternative approach for correcting blood-related diseases is the direct intravenous administration of viral vectors, so called in vivo gene therapy. In this study we evaluated the safety and efficacy of in vivo gene therapy using a foamy virus vector for the correction of canine SCID-X1. In newborn SCID-X1 dogs, injection of a foamy virus vector expressing the human IL2RG gene resulted in an expansion of lymphocytes expressing the common gamma chain and the development of CD3(+) T lymphocytes. CD3(+) cells expressed CD4 and CD8 co-receptors, underwent antigen receptor gene rearrangement and demonstrated functional maturity in response to T cell mitogens. Retroviral integration site analysis in four animals revealed a polyclonal pattern of integration in all dogs with evidence for dominant clones. These results demonstrate that a foamy virus vector can be administered with therapeutic benefit in the SCID-X1 dog, a clinically relevant preclinical model for in vivo gene therapy.