Nonviral gene delivery using PAMAM dendrimer conjugated with the nuclear localization signal peptide derived from human papillomavirus type 11 E2 protein

J Biomater Sci Polym Ed. 2021 Jun;32(9):1140-1160. doi: 10.1080/09205063.2021.1909411. Epub 2021 Apr 19.

Abstract

Polyamidoamine (PAMAM) dendrimers are biocompatible polymers utilized in multiple biomedical applications including tissue engineering, medical diagnosis, drug and gene delivery systems, and biosensors. Normally, high-generation PAMAM dendrimers are advantageous for use in gene therapy research because they have a relatively high transfection efficiency. A high-generation PAMAM dendrimer has a high charge density, which induces greater damage to the membranous organelles than that induced by a low-generation PAMAM dendrimer. In this study, we added NLS sequences derived from the human papillomavirus (HPV) type 11 E2 protein to the low-generation PAMAM generation 2 (PAMAM G2) dendrimer and simultaneously introduced histidine residues to reduce cytotoxicity. RKRARH-PAMAM G2 showed similar and high transfection efficiencies in Neuro-2A and NIH3T3 cell lines and relatively low cytotoxicities relative to that of polyethylenimine 25 kDa (PEI 25 kDa).

Keywords: Cationic polymer; histidine; human papillomavirus type 11 E2 protein; nonviral vector; nuclear localization signal (NLS); polyamidoamine (PAMAM) dendrimer; transfection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Dendrimers*
  • Gene Transfer Techniques
  • Genetic Therapy
  • Human papillomavirus 11
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Nuclear Localization Signals*
  • Polyamines

Substances

  • Dendrimers
  • Nuclear Localization Signals
  • PAMAM Starburst
  • Poly(amidoamine)
  • Polyamines