A quantitative nonimmunogenic transgene product for evaluating vectors in nonhuman primates.
The success of gene therapy depends on safe, effective vectors to transfer genetic information. We have developed a means to quantitatively assess efficacy of gene transfer vectors by using a biologically inert, secreted reporter molecule, the beta chain of chorionic gonadotropin (beta-CG). Using an isogenic beta chain subunit of CG in a recombinant adeno-associated virus (rAAV) vector, overall gene transfer of rhesus macaque muscle is demonstrated over time by measuring the serum concentration of beta-CG. Endogenous levels of gonadotropins are not detectable in healthy, nonpregnant primates as confirmed by the inability to detect serum levels of beta-CG prior to vector administration. The serum concentration of beta-CG also provides a measure for the transfer efficiency in liver and/or muscle in immunodeficient mice using recombinant adenovirus and rAAV vectors. No biological effect was observed in animals tested. Assaying for the serum level of beta-CG serves as a surrogate quantitative marker of gene transfer without interfering with the biology of the host or transduction process.
Zoltick
P W
PW
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania and The Wistar Institute, Philadelphia, Pennsylvania, 19104, USA.
Wilson
J M
JM
D000818:Animals; D006063:Chorionic Gonadotropin / Q000097:blood / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D005822:Genetic Vectors; D008253:Macaca mulatta; D019076:Transgenes
D006063:Chorionic Gonadotropin