Long-term transgene expression by administration of a lentivirus-based vector to the fetal circulation of immuno-competent mice

Highly efficient EIAV-mediated in utero gene transfer and expression in the major muscle groups affected by Duchenne muscular dystrophy

“…14 In this study, we have extended our previous in utero investigations to achieve widespread gene transfer and expression in several muscle groups important to the treatment of DMD. Using intraperitoneal, intrathoracic, supracostal, intramuscular and systemic routes of injection, we show that the EIAV vector can efficiently transduce muscle cells of the diaphragm and abdominal cavity, the intercostal muscles and the skeletal musculature of all injected limbs as well as the heart muscle.…”

“…administration of VSV-G pseudotyped SMART2 Z. 14 Maintenance of gene expression is most likely due to integration of the vector into the host genome and negligible degeneration of myofibres in MF-1 mice. These data are in agreement with recently published literature.…”

“…All tissues examined were, in varying degrees, positive for EIAV vector presence with the exception of the pancreas, white blood cells and notably the sperm. 14 Importantly for an integrating vector, despite continued expression of the transgene in fetally treated male and female adult mice their progeny show no expression of the transgene. Lentiviral vectors have previously been reported to transduce haematopoietic stem cells 17,18 and in our studies using VSV-G pseudotyped EIAV, cells of the bone marrow have been shown to be positive for vector presence by PCR analysis.…”

“…LG Gregory et al adenovirus vector encoding factor IX, 14 by readministration of vector to fetally treated adults. Expression of dystrophin or minidystrophin in fetal myofibres after in utero gene delivery would prevent the repeated rounds of necrosis and associated inflammation observed in dystrophic muscle where dystrophin expression is totally lacking and avoid, or at least limit, the early onset of myodegeneration.…”

Reduced toxicity of F-deficient Sendai virus vector in the mouse fetus

“…In contrast, the liver and heart were the principle sites of marker gene expression after the injection of adenovirus 16 and lentivirus. 17 Intramuscular and intraperitoneal injection of lentivirus results in strong gene expression in local myocytes and those of the abdominal wall and diaphragm, respectively. 10 In contrast, intraperitoneal SeVV results in mesothelial expression; intramuscular injection results in the staining of cells other than myocytes, perhaps connective tissue.…”