Foetal gene delivery in mice by intra-amniotic administration of retroviral producer cells and adenovirus

Nonviral gene transfer into fetal mouse livers (a comparison between the cationic polymer PEI and naked DNA)

“…3 In the last years, gene transfer into fetuses of various animals has primarily utilized viral vectors. [4][5][6][7] However, since viral vectors often exhibit side-effects, 8,9 safety concerns have led to the investigation of nonviral vectors as alternative approaches. 10,11 In the present study, the cationic polymer polyethylenimine (PEI) was used for intrauterine gene transfer.…”

Adenovirus-mediated prenatal gene transfer to murine central nervous system

“…There is no significant inflammatory reaction observed in the brain, liver or other organs histologically. Previous studies also indicated that little immune response occurs in fetal rodents 8,10 compared with other species such as sheep and rabbit, in which significant inflammatory response was observed. 21,22 Thus the non-integrative property of adenovirus vector tends to play an important role in the decrement of transgene expression.…”

“…Studies on prenatal gene transfer showed that gene transduction was achieved in many organs such as the lung, [6][7][8] the digestive tract, 7 the liver [9][10][11][12] and the heart 9,10 via various routes such as intra-amniotic, [6][7][8] intraplacental, 9 into yolk sac vessels 10 and directly to the embryo. 11,12 Recombinant adenovirus was the most often used vector because of its advantages in prenatal gene transfer, such as having a broad host range, the relative easiness in obtaining high titers and its powerfulness in gene transduction and expression.…”

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

“…The liver and other organs were placed in 100% ethanol for 2 h before staining for b-galactosidase transgene expression using X-gal solution. 2 Tissue was fixed in 10% formaldehyde solution, paraffin embedded, sectioned, and counterstained with neutral red.…”

“…They have been used in several fetal studies in different animal models to explore various application routes and have demonstrated successful transgene expression in the fetal airways, gut, liver, adrenal glands, and vascular system. [2][3][4][5][6][7][8][9][10][11][12][13][14] Their immunogenicity has been exploited to study the possibility of fetal immune tolerance after prenatal administration. [15][16][17] However, loss of these episomal DNA vectors during subsequent cell divisions following infection severely curtails their applicability to long-term fetal gene therapy.…”