Analysis of testes and semen from rabbits treated by intravenous injection with a retroviral vector encoding the human factor VIII gene: no evidence of germ line transduction.
作者： Holger H. Roehl , Martha E. I. Leibbrandt , Judith S. Greengard , Edgar Kamantigue , William G. Glass
DOI: 10.1089/10430340050208000
关键词: Genetic enhancement 、 Andrology 、 Pathology 、 Virus 、 Gene expression 、 Biology 、 Cell culture 、 Viral vector 、 Testicle 、 Spermatogenesis 、 Semen
摘要: In a phase 1 clinical trial, we are evaluating murine leukemia virus (MuLV)-based retroviral vector encoding the human factor VIII gene [hFVIII(V)], administered intravenously, as therapy for hemophilia A. Preclinical biolocalization studies in adult rabbits revealed vector-specific PCR signals testis tissue at low levels. follow-up animal used to (1) estimate frequency with which given cell is transduced, and (2) determine whether positive signal could be detected semen samples from animals treated hFVIII(V). Using 99% confidence bound, results indicate that probability within was transduced less than 1/709,000 (97 days after treatment). This decreased time hFVIII(V) administration. Moreover, rate of provector sequence detection collected weekly throughout two cycles spermatogenesis 3/4281 reactions (0.07%), lower false positives (1/800, 0.125%) observed control animals. assays single-copy sensitivity, have shown small number cells present does not give rise detectable semen.
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