Basic peptides as functional components of non-viral gene transfer vehicles

Mahito Nakanishi, Akiko Eguchi, Teruo Akuta, Emi Nagoshi, Shigeo Fujita, Jun Okabe, Takao Senda, Mamoru Hasegawa

Research output: Contribution to journalReview ArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Improving the performance of non-viral gene-delivery vehicles that consist of synthetic compounds and nucleic acids is a key to successful gene therapy. Supplementing synthetic vehicles with various biological functions by using natural or artificial peptides is a promising approach with which to achieve this goal. One of the obstacles hindering this effort is that some of the potentially useful peptides, especially those with many basic amino acid residues, interfere with the formation of the complex owing to strong electrostatic interactions with the nucleic acid. In this review, we describe our recent work in examining the potential of these peptides in gene delivery, using a recombinant lambda phage particle as the model for the gene-delivery complex. Lambda phage encapsulates large duplex DNA in a rigid polyplex-like shell with a diameter of 55 nm, and can display various peptides on this capsid, independently of particle formation. By examining the expression of marker genes encapsulated in the phage capsid, we have demonstrated that the protein transduction domain of HIV Tat protein and the nuclear localization signal derived from SV40 T antigen can remarkably facilitate the delivery of these marker genes across the two major barriers, the cell membrane and the nuclear membrane, respectively. Our results indicate that these basic peptides can constitute effective components of synthetic gene-transfer complexes, as long as sufficient copies are displayed on the outer surface of the complex.

Original languageEnglish
Pages (from-to)141-150
Number of pages10
JournalCurrent Protein and Peptide Science
Volume4
Issue number2
DOIs
Publication statusPublished - Apr 2003
Externally publishedYes

Keywords

  • Cell membrane
  • Gene delivery system
  • Lambda phage
  • Nuclear localization signal (NLS)
  • Nuclear membrane
  • Phage display system
  • Polyplex
  • Protein transduction domain (PTD)

Cite this