title: Secreted antiviral entry inhibitory (SAVE) peptides for gene therapy of HIV infection.
abstract: Gene therapeutic strategies for human immunodeficiency virus type 1 (HIV-1) infection could potentially overcome the limitations of standard antiretroviral drug therapy (ART). However, in none of the clinical gene therapy trials published to date, therapeutic levels of genetic protection have been achieved in the target cell population for HIV-1. To improve systemic antiviral efficacy, C peptides, which are efficient inhibitors of HIV-1 entry, were engineered for high-level secretion by genetically modified cells. The size restrictions for efficient peptide export through the secretory pathway were overcome by expressing the C peptides as concatemers, which were processed into monomers by furin protease cleavage. These secreted antiviral entry inhibitory (SAVE) peptides mediated a substantial protective bystander effect on neighboring nonmodified cells, thus suppressing virus replication even if only a small fraction of cells was genetically modified. Accordingly, these SAVE peptides may provide a strong benefit to AIDS patients in future, and, if applied by direct in vivo gene delivery, could present an effective alternative to antiretroviral drug regimen.
authors.affiliation: Department of Hygiene, Microbiology and Social Medicine, Division of Virology, Innsbruck Medical University, Innsbruck, Austria. lisa.egerer@i-med.ac.at
authors.forename: Lisa
authors.initials: L
authors.lastname: Egerer
authors.forename: Andreas
authors.initials: A
authors.lastname: Volk
authors.forename: Joerg
authors.initials: J
authors.lastname: Kahle
authors.forename: Janine
authors.initials: J
authors.lastname: Kimpel
authors.forename: Frances
authors.initials: F
authors.lastname: Brauer
authors.forename: Felix G
authors.initials: FG
authors.lastname: Hermann
authors.forename: Dorothee
authors.initials: D
authors.lastname: von Laer
mesh_terms: D015153:Blotting, Western; D002096:C-Peptide / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D017988:Gammaretrovirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000235:genetics / Q000628:therapy*; D006801:Humans; D047468:Immunoprecipitation; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D002096:C-Peptide; D010455:Peptides