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Regulation of Angiogenesis and Blood Supply01:24

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
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Programming Stem Cells for Therapeutic Angiogenesis Using Biodegradable Polymeric Nanoparticles
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Gene delivery nanoparticles to modulate angiogenesis.

Jayoung Kim1, Adam C Mirando2, Aleksander S Popel2

  • 1Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center and Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

Advanced Drug Delivery Reviews
|December 4, 2016
PubMed
Summary

Gene therapy using non-viral nanoparticles offers a promising approach to correct imbalanced angiogenesis, a key factor in many diseases. Further nanoparticle design improvements are crucial for effective clinical translation in treating conditions like cancer and macular degeneration.

Keywords:
Age-related macular degenerationChitosanCholesterolGene therapyIschemiaN-[1-(2.3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfateNon-viralPoly(beta-amino ester)Poly(ethylene imine)Poly(l-lysine)Poly(lactic-co-glycolic) acidPoly(vinyl pyrrolidone)-cyclodextrinPolymeric nanoparticlesTissue engineeringTumorWound healing

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Area of Science:

  • Biomedical Engineering
  • Molecular Biology
  • Gene Therapy

Background:

  • Angiogenesis, the formation of new blood vessels, is a tightly regulated process.
  • Imbalances in pro- and anti-angiogenic factors lead to aberrant angiogenesis, contributing to diseases like cancer and wet age-related macular degeneration.
  • Gene therapy presents a potential strategy to restore angiogenic balance by modulating gene expression.

Purpose of the Study:

  • To review key factors targeted in angiogenesis gene therapy.
  • To summarize non-viral nanoparticle-mediated gene delivery approaches for therapeutic angiogenesis.
  • To discuss recent gene therapy applications and propose enhanced nanoparticle design strategies.

Main Methods:

  • Literature review of gene therapy strategies for angiogenesis.
  • Analysis of non-viral nanoparticle delivery systems.
  • Examination of pre-clinical and clinical trial data for various diseases.

Main Results:

  • Gene therapy can engineer neovascularization in both pro- and anti-angiogenic directions.
  • Non-viral nanoparticles show potential but face challenges in safety, delivery efficiency, and therapeutic outcomes.
  • Successful applications exist in preclinical and clinical studies for ischemia, tissue regeneration, cancer, and wet age-related macular degeneration.

Conclusions:

  • Non-viral nanoparticle-mediated gene therapy is a viable strategy for modulating angiogenesis.
  • Overcoming current limitations through enhanced nanoparticle design is essential for clinical translation.
  • Targeted gene therapy holds significant promise for treating angiogenesis-related diseases.