3PO, a novel nonviral gene delivery system using engineered Ad5 penton proteins

L. K. Medina-Kauwe, N. Kasahara, L. Kedes

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

This study describes the development of 3PO, a nonviral, protein-based gene delivery vector which utilizes the highly evolved cell-binding, cell-entry and intracellular transport functions of the adenovirus serotype 5 (Ad5) capsid penton protein. A penton fusion protein containing a polylysine sequence was produced by recombinant methods and tested for gene delivery capability. As the protein itself is known to bind integrins through a conserved consensus motif, the penton inherently possesses the ability to bind and enter cells through receptor-mediated internalization. The ability to lyse the cellular endosome encapsulating internalized receptors is also attributed to the penton. The recombinant protein gains the additional function of DNA binding and transport with the appendage of a polylysine motif. This protein retains the ability to form pentamers and mediates delivery of a reporter gene to cultured cells. Interference by oligopeptides bearing the integrin binding motif suggests that delivery is mediated specifically through integrin receptor binding and internalization. The addition of protamine to penton-DNA complexes allows gene delivery in the presence of serum.

Original languageEnglish (US)
Pages (from-to)795-803
Number of pages9
JournalGene Therapy
Volume8
Issue number10
DOIs
StatePublished - Jun 18 2001

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Keywords

  • 3PO
  • Adenovirus
  • Gene therapy
  • PBK10
  • Penton
  • Protamine

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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