CD44 Mediated Nonviral Gene Delivery into Human Embryonic Stem Cells via Hyaluronic-Acid-Coated Nanoparticles

Jonathan Yen, Hanze Ying, Hua Wang, Lichen Yin, Fatih Uckun, Jianjun Cheng

Research output: Contribution to journalArticlepeer-review

Abstract

Gene delivery is an important tool to study and manipulate human pluripotent stem cells for regenerative medicine purposes. Yet current methods of transient gene delivery to stem cells are still inefficient. Through the combination of biologically based concepts and material design, we aim to develop new methods to enhance the efficiency of gene delivery to stem cells. Specifically, we use poly(γ-4-(((2-(piperidin-1-yl)ethyl)amino)methyl)benzyl-l-glutamate) (PVBLG-8), a membrane-active helical, cationic polypeptide, to condense plasmid DNA to form stable nanocomplexes, which are further coated with hyaluronic acid (HA). HA not only shields the positive charges of PVBLG-8 to reduce toxicity, but also acts as a targeting moiety for cell surface receptor CD44, which binds HA and facilitates the internalization of the nanocomplexes. Upon entering cells, HA is degraded by hyaluronidase in endosomes and PVBLG-8 is exposed, facilitating the endosomal escape of DNA/polypeptide complex. Our studies show that the coating of HA significantly increases gene transfection efficiency of DNA/PVBLG-8 nanocomplexes from about 28 to 36% with largely reduced toxicity.

Original languageEnglish (US)
Pages (from-to)326-335
Number of pages10
JournalACS Biomaterials Science and Engineering
Volume2
Issue number3
DOIs
StatePublished - Mar 14 2016

Keywords

  • CD44
  • human embryonic stem cells
  • human pluripotent stem cells
  • hyaluronic acid
  • nonviral gene delivery
  • polypeptides

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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