Pw. Zoltick et Jm. Wilson, A quantitative nonimmunogenic transgene product for evaluating vectors in nonhuman primates, MOL THER, 2(6), 2000, pp. 657-659
The success of gene therapy depends on safe, effective vectors to transfer
genetic information. We have developed a means to quantitatively assess eff
icacy of gene transfer vectors by using a biologically inert, secreted repo
rter molecule, the beta chain of chorionic gonadotropin (beta -CG). Using a
n isogenic beta chain subunit of CG in a recombinant adeno-associated virus
(rAAV) vector, overall gene transfer of rhesus macaque muscle is demonstra
ted 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 immunodeficie
nt mice using recombinant adenovirus and rAAV vectors. No biological effect
was observed in animals tested. Assaying for the serum level of beta -CG s
erves as a surrogate quantitative marker of gene transfer without interferi
ng with the biology of the host or transduction process.