Xh. Ye et al., EVALUATING THE POTENTIAL OF GERM-LINE TRANSMISSION AFTER INTRAVENOUS ADMINISTRATION OF RECOMBINANT ADENOVIRUS IN THE C3H MOUSE, Human gene therapy, 9(14), 1998, pp. 2135-2142
Citations number
17
Categorie Soggetti
Genetics & Heredity","Biothechnology & Applied Migrobiology","Medicine, Research & Experimental
The goal of this study is to assess the likelihood that an adenoviral
vector disseminated to gonads will be transmitted to offspring. This s
tudy is based on the observation that systemically administered vector
can be detected in both ovaries and testes, using sensitive nested PC
R techniques, Although the extent of vector dissemination to gonads is
extremely small, as it is detectable only by nested PCR, it is unclea
r where it is located within these tissues and whether the DNA is capa
ble of integration and transmission to offspring, A protocol was devel
oped in C3H mice to address this question. Both male and female C3H mi
ce were injected with a high dose of H5.001CBhOTC, an E1- and E4-delet
ed vector expressing human ornithine transcarbamylase. This dose of ve
ctor was sufficient to target 80% of hepatocytes (Gao et al,, J, Virol
, 1996; 70:8934-8943) and disseminate, at low levels, to both ovaries
and testes in 94% of animals as determined by PCR, Vector-administered
animals and controls were mated and 814 offspring were evaluated for
germ line transmission of the adenoviral vector by DNA hybridization o
f total cellular DNA extracted from the fetus. Southern blot analysis
showed no evidence of germ line transmission in 578 offspring of cross
es in which either one or both parents received recombinant adenovirus
.