Cell-permeable peptides improve cellular uptake and therapeutic gene delivery of replication-deficient viruses in cells and in vivo

Nat Med. 2003 Mar;9(3):357-62. doi: 10.1038/nm835. Epub 2003 Feb 24.

Abstract

Small polybasic peptides derived from the transduction domains of certain proteins, such as the third alpha-helix of the Antennapedia (Antp) homeodomain, can cross the cell membrane through a receptor-independent mechanism. These cell-permeable molecules have been used as 'Trojan horses' to introduce biologically active cargo molecules such as DNA, peptides or proteins into cells. Using these cell-permeable peptides, we have developed an efficient and simple method to increase virally mediated gene delivery and protein expression in vitro and in vivo. Here, we show that cell-permeable peptides increase viral cell entry, improve gene expression at reduced titers of virus and improve efficacy of therapeutically relevant genes in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Amino Acid Sequence
  • Animals
  • Antennapedia Homeodomain Protein
  • Arteries / cytology
  • Arteries / metabolism
  • COS Cells
  • Fluorescent Dyes / metabolism
  • Gene Expression Regulation
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Hindlimb / blood supply
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Ischemia
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Nuclear Proteins*
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Transcription Factors*
  • Virus Replication* / physiology*

Substances

  • Antennapedia Homeodomain Protein
  • Fluorescent Dyes
  • Homeodomain Proteins
  • Nuclear Proteins
  • Peptides
  • Recombinant Fusion Proteins
  • Transcription Factors
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III