HIV-1-derived lentiviral vectors and fetal route of administration on transgene biodistribution and expression in rhesus monkeys

Transfer of Therapeutic Genes into Fetal Rhesus Monkeys Using Recombinant Adeno-Associated Type I Viral Vectors

“…In a prior study using HIV-1-derived lentiviral vectors, a quantitative real-time PCR assay was used to calculate the level of lentiviral transduction and the eGFP mRNA transcripts in transduced tissues. 6 This prior study focused on direct comparisons between fetuses under a variety of experimental conditions, including gene transfer at different gestational ages using different routes of administration and lentiviral vector constructs. The findings from these studies were similar to those in the study described herein, namely that i.p.…”

“…5 Studies have also shown the efficiency of lentiviral vector-mediated gene transfer in fetal monkeys using both systemic and organ-targeting approaches. [6][7][8][9] These studies have indicated that intraperitoneal (i.p.) administration of reporter genes (e.g., enhanced green fluorescent protein [eGFP] or firefly luciferase) in early gestation results in long-term transgene expression in the muscular component of the diaphragm and peritoneum.…”

“…administration of reporter genes (e.g., enhanced green fluorescent protein [eGFP] or firefly luciferase) in early gestation results in long-term transgene expression in the muscular component of the diaphragm and peritoneum. [6][7][8][9] This study used a similar technique for early gestation fetal gene delivery of rAAV type 1 expressing human GAA (rAAV1-CMV-hGAA), human a-1-antitrypsin (rAAV1-CBA-hAAT), or minidystrophin (rAAV1-CMV-miniDMD). The results show high levels of hGAA, hAAT, or DMD expression within the muscular component of the diaphragm and peritoneum in treated animals, without any evidence of adverse effects.…”

Fetal Gene Therapy

“…It was not surprising, therefore, when we examined other tissues of the recipients, to find that gene transfer was not limited to cells of the hematopoietic system, but had occurred in essentially all of the organs we examined, including numerous cell types within the liver, lung, and brain [79,81,82,86]. Concomitantly, in utero gene transfer studies performed by other investigators in sheep, rodent, and non-human primate models employing a variety of viral-based gene delivery vectors produced similar results [78][79][80][81][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105], raising the exciting possibility that in utero gene therapy could potentially be used to treat not only hematologic disorders, but also numerous genetic disorders that affect tissues other than the hematopoietic system. For example, in the case of the hemophilias, this method could likely be used with success to delivering genes for the missing coagulation factors to the developing liver at levels that would covert patients with severe hemophilia to a moderate or even mild phenotype [79].…”

Renal Tissue Engineering with Decellularized Rhesus Monkey Kidneys: Age-Related Differences

“…13 Briefly, kidney transverse sections were washed twice with phosphate-buffered saline (PBS) (Gibco, Invitrogen) followed by a decellularization solution of 1% (v/v) sodium dodecyl sulfate (Invitrogen) diluted in distilled water at 4°C. The solution was changed 8 h after initial tissue harvest and then every 48 h until the tissue was transparent (7-10 days).…”