A quantitative nonimmunogenic transgene product for evaluating vectors in nonhuman primates

Citation
Pw. Zoltick et Jm. Wilson, A quantitative nonimmunogenic transgene product for evaluating vectors in nonhuman primates, MOL THER, 2(6), 2000, pp. 657-659
Citations number
5
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR THERAPY
ISSN journal
15250016 → ACNP
Volume
2
Issue
6
Year of publication
2000
Pages
657 - 659
Database
ISI
SICI code
1525-0016(200012)2:6<657:AQNTPF>2.0.ZU;2-A
Abstract
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.