Enhanced in vivo gene transfer into the placenta using RGD fiber-mutant adenovirus vector

Katayama, Kazufumi; Furuki, Rie; Yokoyama, Hisayuki; Kaneko, Makoto; Tachibana, Masashi; Yoshida, Ichiro; Nagase, Hisamitsu; Tanaka, Keiichi; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Nakagawa, Shinsaku; Nakanishi, Takashi

doi:10.1016/j.biomaterials.2011.02.038

Cited by 16 publications

(9 citation statements)

References 50 publications

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“…In the pre-clinical studies of Ad.VEGF placental gene transfer, local delivery to the uterine arteries has been achieved either by direct injection combined with proximal occlusion of the vessel or by external application of a thermolabile Pluronic gel to the vessel wall. Maternal intravascular gene therapy using an adenoviral vector gives transgenic protein expression only in the placenta and not in the fetus, when given to pregnant sheep (50,51), mice (52), and guinea pigs (37), In contrast, adenoviral vector injection into the placenta of rabbits or rats transduces both the placenta and the fetus (53,54). Exposure of human placental villous explants to high dose adenoviral vector showed that, where the syncytiotrophoblast was deficient there was occasional transduction of the underlying cytotrophoblast, but no evidence of the vector crossing the basement membrane (55).…”

Section: Risks Of Placental Directed Gene Therapy (B) Placental Transmentioning

confidence: 99%

Placenta-directed gene therapy for fetal growth restriction

Krishnan

David

2017

Seminars in Fetal and Neonatal Medicine

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Fetal growth restriction (FGR) is a serious pregnancy complication affecting ∼8% of all pregnancies. There is no treatment to increase fetal growth in the uterus. Gene therapy presents a promising treatment strategy for FGR, with the use of adenoviral vectors encoding for proteins such as vascular endothelial growth factor (VEGF) and insulin-like growth factor demonstrating improvements in fetal growth, placental function, and neonatal outcome in preclinical studies. Safety assessments suggest no adverse risk to the mother or fetus for VEGF maternal gene therapy; a clinical trial is in development. This review assesses research into placenta-directed gene therapy for FGR, investigating the use of transgenes and vectors, their route of administration in obstetrics, and the steps that will be needed to take this treatment modality into the clinic.

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Section: Risks Of Placental Directed Gene Therapy (B) Placental Transmentioning

confidence: 99%

Placenta-directed gene therapy for fetal growth restriction

Krishnan

David

2017

Seminars in Fetal and Neonatal Medicine

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“…Proteins containing an RGD sequence, together with the integrins that serve as receptors for the sequence, constitute a major recognition system for cell adhesion. The RGD motif has high affinity for αv integrins on tumor cells and has been used for the purpose of actively targeting vectors to deliver drugs or genes into tumor cells (4). Certain studies have adopted RGD-modified polymers or lipids as non-viral vectors for the targeted delivery of genetic material to achieve efficient cancer gene therapy, including antiangiogenic therapy (2,5–7).…”

Section: Introductionmentioning

confidence: 99%

Construction of a tumor cell-targeting non-viral gene delivery vector with polyethylenimine modified with RGD sequence-containing peptide

Xing¹,

Pan

Fang

et al. 2013

Oncology Letters

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The objective of the present study was to construct a novel type of non-viral gene delivery vector with high delivery efficiency and specific tumor cell-targeting ability. The CP9 peptide (CYGGRGDTP) containing Arg-Gly-Asp sequence was employed to be conjugated onto polyethylenimine (PEI) to act as the role of the targeting moiety. The chemical linker, N-succinimidyl-3-(2-pyridyldithio) propionate, was applied during the synthesis of the vector (CP9-PEI). The physicochemical characteristics of the vector were evaluated by the methods of 1H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, gel retardation assay, electron microscope observation and particle size detection. HepG2 cells were used to verify the gene delivery efficiency and targeting ability by gene delivery procedure and free CP9 peptide inhibition tests. The results showed that the successful synthesis of CP9-PEI and the synthesized vector may efficiently condense plasmid DNA into round particles with diameters of ~200 nm at a polymer/pDNA ratio of 10. CP9-PEI may deliver the reporter gene into HepG2 cells with higher efficiency and the efficiency may be inhibited by the free CP9 peptide. The present study suggested that the modification of PEI with the CP9 peptide is an effective method to construct a novel tumor cell-targeting non-viral vector, and that the novel vector exhibits great prospect in the field of cancer gene therapy.

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“…Ad vectors containing this RGD peptide in the HI loop of the fiber showed higher yields of gene transfer than vectors containing the identical peptide attached at the fiber‘s C-terminus, due to the easy access to the receptor [39,101,102]. Many groups transduced effectively different types of tumor cells by inserting this RGD motif into the HI loop of the Ad fiber in vitro [103] and in vivo [104,105]. Rojas et al .…”

Section: Methods To Alter the Natural Ad Vector Tropismmentioning

confidence: 99%

Peptide-Based Technologies to Alter Adenoviral Vector Tropism: Ways and Means for Systemic Treatment of Cancer

Reetz

Herchenröder

Pützer

2014

Viruses

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Due to the fundamental progress in elucidating the molecular mechanisms of human diseases and the arrival of the post-genomic era, increasing numbers of therapeutic genes and cellular targets are available for gene therapy. Meanwhile, the most important challenge is to develop gene delivery vectors with high efficiency through target cell selectivity, in particular under in situ conditions. The most widely used vector system to transduce cells is based on adenovirus (Ad). Recent endeavors in the development of selective Ad vectors that target cells or tissues of interest and spare the alteration of all others have focused on the modification of the virus broad natural tropism. A popular way of Ad targeting is achieved by directing the vector towards distinct cellular receptors. Redirecting can be accomplished by linking custom-made peptides with specific affinity to cellular surface proteins via genetic integration, chemical coupling or bridging with dual-specific adapter molecules. Ideally, targeted vectors are incapable of entering cells via their native receptors. Such altered vectors offer new opportunities to delineate functional genomics in a natural environment and may enable efficient systemic therapeutic approaches. This review provides a summary of current state-of-the-art techniques to specifically target adenovirus-based gene delivery vectors.

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Enhanced in vivo gene transfer into the placenta using RGD fiber-mutant adenovirus vector

Cited by 16 publications

References 50 publications

Placenta-directed gene therapy for fetal growth restriction

Placenta-directed gene therapy for fetal growth restriction

Construction of a tumor cell-targeting non-viral gene delivery vector with polyethylenimine modified with RGD sequence-containing peptide

Peptide-Based Technologies to Alter Adenoviral Vector Tropism: Ways and Means for Systemic Treatment of Cancer

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