Angiographically guided utero-placental gene transfer in rabbits with adenoviruses, plasmid/liposomes and plasmid/polyethyleneimine complexes

Heikkilä, Annaleena; Hiltunen, Mikko; Turunen, Mikko P.; Keski‐Nisula, Leea; Turunen, Anna-Mari; Räsänen, Heikki; Rissanen, Tuomas T.; Kosma, Veli‐Matti; Manninen, Hannu; Heinonen, Seppo; Ylä‐Herttuala, Seppo

doi:10.1038/sj.gt.3301444

Cited by 23 publications

(14 citation statements)

References 22 publications

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“…It is however reassuring that angiographic injection of adenovirus vectors containing the LacZ marker gene into rabbit UtAs was shown to be safe in one study, and produced high levels of transfection in the placental trophoblast; importantly, there was only low level leakage of vector into the fetus. 33 Severe early onset FGR affects 1:500 pregnancies, and is associated with high perinatal mortality and long-term complications in survivors. An affected fetus may never achieve a viable delivery weight (500 g) and the parents face a stark choice between termination of pregnancy, or allowing the fetus to die in utero, as there are no therapies available.…”

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confidence: 99%

Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep

et al. 2008

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confidence: 99%

Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep

et al. 2008

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“…10 Angiographically guided uteroplacental gene transfer with adenoviruses and plasmid vectors in rabbits resulted in a very high local transfection efficiency of placental trophoplastic cells. This led us to investigate whether the same approach would also affect germline cells.…”

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confidence: 99%

Transfection of oocytes and other types of ovarian cells in rabbits after direct injection into uterine arteries of adenoviruses and plasmid/liposomes

et al. 2003

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“…( P B S ) in the positive tissues could be due to a low expression level of the LacZ gene, below the sensitivity of the X-gal staining, in some unstained regions, as has been recently shown in a rabbit model of angiographically guided uteroplacental gene transfer [18] . The other tissues harvested, lung and kidney, were consistently negative for the presence and expression of the reporter transgene (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Feasibility of Retroviral Vector-Mediated in utero Gene Transfer to the Fetal Rabbit

Moreno

Rosal²,

Cabero³

et al. 2005

Fetal Diagn Ther

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Objectives: Successful treatment or prevention of severe hereditary diseases could conceivably be achieved by genetic intervention early in development. Viral vector-mediated fetal gene transfer is proving a valuable tool to test the above concept in relevant animal models. Although the pregnant rabbit is a well-recognized model for fetal therapy, few preclinical assays have used it to validate fetal gene transfer approaches. In this preliminary study we assessed for the first time the feasibility of retroviral vector-mediated in utero gene transfer in the fetal rabbit. Methods: Different amounts of the vesicular stomatitis virus G pseudotyped MFG(nls)LacZ retroviral vector, expressing a nuclear-localized β-galactosidase reporter protein were injected intraperitoneally and -hepatically into 20- to 22-day-old fetuses. At 8–9 days post-treatment, the pups were sacrificed and the tissues harvested for analysis. Evidence of gene transfer was obtained by PCR amplification of proviral sequences within genomic DNA isolated from the treated samples. Transgenic β-galactosidase expression was assessed by X-gal histochemical staining. Results: By intraperitoneal injection 43% of the viable fetuses treated (3/7) showed evidence of successful LacZ gene transfer and low-level β-galactosidase expression into liver and heart, whereas by intrahepatic injection roughly 38% (3/8) of the livers were positive for LacZ gene transfer and expression. The success rate for the viable fetuses rose to 67% positive livers (4/6) when a near double amount of recombinant virus was injected using a 10-fold concentrated virus stock. In terms of short-term safety, fetal and maternal survival rates approached 80% of treated fetuses, and 100% of treated does. Conclusions: The pregnant rabbit is a useful and reliable model allowing the design of further studies to optimize the conditions for effective, safer, and persistent retroviral vector-mediated fetal gene transfer.

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Angiographically guided utero-placental gene transfer in rabbits with adenoviruses, plasmid/liposomes and plasmid/polyethyleneimine complexes

Cited by 23 publications

References 22 publications

Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep

Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep

Transfection of oocytes and other types of ovarian cells in rabbits after direct injection into uterine arteries of adenoviruses and plasmid/liposomes

Feasibility of Retroviral Vector-Mediated in utero Gene Transfer to the Fetal Rabbit

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