Cell-permeable peptides improve cellular uptake and therapeutic gene delivery of replication-deficient viruses in cells and in vivo.
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.
Gratton
Jean-Philippe
JP
Department of Pharmacology, Vascular Cell Signaling and Therapeutics Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Yu
Jun
J
Griffith
Jason W
JW
Babbitt
Roger W
RW
Scotland
Ramona S
RS
Hickey
Reed
R
Giordano
Frank J
FJ
Sessa
William C
WC
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D051943:Antennapedia Homeodomain Protein; D001158:Arteries / Q000166:cytology / Q000378:metabolism; D019556:COS Cells; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006614:Hindlimb / Q000098:blood supply; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007511:Ischemia; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009687:Nuclear Proteins; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors; D014779:Virus Replication / Q000502:physiology*
D051943:Antennapedia Homeodomain Protein; D005456:Fluorescent Dyes; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III