Simple and highly efficient method for transient in vivo gene transfer to mid-late pregnant mouse uterus

Koyama, Shinsuke; Kimura, Tadashi; Ogita, Kazuhide; Nakamura, Hitomi; Tabata, Chisa; Khan, Md. Abu Hadi Noor Ali; Temma-Asano, Kumiko; Shimoya, Koichiro; Tsutsui, Tateki; Koyama, Masayasu; Kaneda, Yasufumi; Murata, Yuji

doi:10.1016/j.jri.2005.12.007

Cited by 12 publications

(9 citation statements)

References 24 publications

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“…Exogenous b-galactosidase activity was detectable in basal lamina of the placenta, decidua and amnion by b-galactosidase staining using X-gal (5-bromo-4-chloro-3-indolyl-b-D-galactopyranoside) as a substrate. Importantly, treatment with our HVJ-E vector transfection system in the mid-term of pregnancy did not alter the course of pregnancy; i.e., the average litter size and average time of parturition were similar between transfected mice and untreated mice [11]. Therefore, the transfection procedure used here did not disturb the normal course of pregnancy.…”

Section: Discussionmentioning

confidence: 81%

“…In our preliminary experiments, luciferase activity in the uterus after pcDNA3-Luc transfection into the extraamniotic cavity at day 14.5 p.c. was the highest at 24 hours after transfection [11]. After 72 hours of transfection, less than 5 % of the peak level of luciferase activity was observed.…”

Section: Discussionmentioning

confidence: 87%

“…We inserted the needle (30 G) into the extraamniotic space between the amniotic sacs, taking care not to rupture the amniotic membranes. Then, the incision was sutured and the mice were allowed to recover [11].…”

Section: Preparation Of Vector-entrapped Plasmid Dnamentioning

confidence: 99%

“…We have established a highly efficient system for transient gene transfer into the early stage of the pregnant mice uterus using hemaggulutinating virus of Japan envelope (HVJ-E) vector [10]. We recently extended this technique to the murine pregnant uterus at the mid-term of pregnancy [11]. Here we injected expression plasmid harboring human VEGF 165 cDNA entrapped by HVJ-E vector into the extraamniotic cavity at day 14.5 post coitus (p.c.)…”

Section: Introductionmentioning

confidence: 99%

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Transient Local Overexpression of Human Vascular Endothelial Growth Factor (VEGF) in Mouse Feto-maternal Interface during Mid-term Pregnancy Lowers Systemic Maternal Blood Pressure

Koyama

Kimura²,

Ogita³

et al. 2006

Horm Metab Res

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The effect on maternal circulation of transient human vascular endothelial growth factor (VEGF) (165) cDNA transfection into the mouse feto-maternal interface at day 14.5 post coitus (p.c.) using a hemagglutinating virus of Japan-envelope (HVJ-E) vector system is reported. On day 15.5 p.c., Western blotting clearly showed overexpression of 18 kD VEGF protein in the uterus. After VEGF transfection, the blood pressure was significantly lowered for 48 hours. On day 17.5 p.c., the blood pressure returned to the control level. Proteinuria was not observed after VEGF transfection. No preterm birth was observed during the course of pregnancy after the transfection procedure. After 24 hours of transfection, human VEGF was not detectable and the mouse VEGF level was similar to that in peripheral blood. However, the soluble fms-like tyrosine kinase (Flt)-1 concentration was significantly lower in VEGF-transfected mice. These results suggest that extraamniotic VEGF overexpression lowered the systemic blood pressure without altering the VEGF concentration in the peripheral blood. Local overexpression of VEGF may become a novel treatment for pregnancy-related disorders such as hypertension complicated-pregnancy and preeclampsia.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 87%

Section: Preparation Of Vector-entrapped Plasmid Dnamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transient Local Overexpression of Human Vascular Endothelial Growth Factor (VEGF) in Mouse Feto-maternal Interface during Mid-term Pregnancy Lowers Systemic Maternal Blood Pressure

Koyama

Kimura²,

Ogita³

et al. 2006

Horm Metab Res

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“…Following administration of plasmid/PEI or plasmid/liposome complexes into the uterine arteries of pregnant rabbits, gene transfer was detected in the placenta and fetuses (37). Injection of virosomes into the extraamniotic space in pregnant mice, however, produced expression in the decidua, basal lamina of the placenta, and amnion, but not in the fetus (115). In contrast, after intravenous administration of liposomes in mice, the vector was not detected in either placental or fetal tissue (110).…”

Section: Placental Transmissionmentioning

confidence: 97%

Gene Therapy for Obstetric Conditions

Spencer

Carr

David

2014

Fet. Matern. Med. Rev.

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The first clinical trials of gene therapy in the 1990s offered the promise of a new paradigm for the treatment of genetic diseases. Over the decades that followed the challenges and setbacks which gene therapy faced often overshadowed any successes. Despite this, recent years have seen cause for renewed optimism. In 2012 Glybera™, an adeno-associated viral vector expressing lipoprotein lipase, became the first gene therapy product to receive marketing authorisation in Europe, with a licence to treat familial lipoprotein lipase deficiency. This followed the earlier licensing in China of two gene therapies: Gendicine™ for head and neck squamous cell carcinoma and Oncorine™ for late-stage nasopharyngeal cancer. By this stage over 1800 clinical trials had been, or were being, conducted worldwide, and the therapeutic targets had expanded far beyond purely genetic disorders. So far no trials of gene therapy have been carried out in pregnancy, but an increasing understanding of the molecular mechanisms underlying obstetric diseases means that it is likely to have a role to play in the future. This review will discuss how gene therapy works, its potential application in obstetric conditions and the risks and limitations associated with its use in this setting. It will also address the ethical and regulatory issues that will be faced by any potential clinical trial of gene therapy during pregnancy.

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In vivo uterine local gene delivery system using TAT‐displaying bionanocapsules

Koizumi

Nakamura

Iijima

et al. 2019

The Journal of Gene Medicine

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BackgroundThe uterus is an organ that is directly accessible via the transvaginal route, whereas the drug delivery system and the gene delivery system (GDS) for the uterus are very limited, even in animal models. In the present study, we optimized a bionanocapsule (BNC) comprising a hepatitis B virus envelope L‐protein particle, for which a structurally similar particle has been used as an immunogen of a conventional HB vaccine worldwide for more than 30 years, as a local uterine GDS using a mouse model.MethodsTo display various antibodies for re‐targeting to different cells other than hepatic cells, the pre‐S1 region of BNC was replaced with a tandem form of the protein A‐derived immunoglobulin G Fc‐interacting region (Z domain, ZZ‐BNC). To induce strong cell adhesion after local administration into the uterine cavity, ZZ‐BNC was modified with a transactivator of transcription (TAT) peptide.ResultsGene transfer using TAT‐modified ZZ‐BNC is approximately 5000‐ or 18‐fold more efficient than the introduction of the same dose of naked DNAs or the use of the cationic liposomes, respectively. TAT‐modified ZZ‐BNC was rapidly eliminated from the uterus and had no effect on the pregnancy rate, litter size or fetal growth.ConclusionsTAT‐modified ZZ‐BNC could be a useful GDS for uterine endometrial therapy via local uterine injection.

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Simple and highly efficient method for transient in vivo gene transfer to mid-late pregnant mouse uterus

Cited by 12 publications

References 24 publications

Transient Local Overexpression of Human Vascular Endothelial Growth Factor (VEGF) in Mouse Feto-maternal Interface during Mid-term Pregnancy Lowers Systemic Maternal Blood Pressure

Transient Local Overexpression of Human Vascular Endothelial Growth Factor (VEGF) in Mouse Feto-maternal Interface during Mid-term Pregnancy Lowers Systemic Maternal Blood Pressure

Gene Therapy for Obstetric Conditions

In vivo uterine local gene delivery system using TAT‐displaying bionanocapsules

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