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Titolo:
Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids
Autore:
Grifman, M; Trepel, M; Speece, P; Gilbert, LB; Arap, W; Pasqualini, R; Weitzman, MD;
Indirizzi:
Salk Inst Biol Studies, Genet Lab, San Diego, CA 92186 USA Salk Inst Biol Studies San Diego CA USA 92186 ab, San Diego, CA 92186 USA Univ Texas, MD Anderson Canc Ctr, Dept GU Med Oncol, Houston, TX 77030 USAUniv Texas Houston TX USA 77030 Dept GU Med Oncol, Houston, TX 77030 USA Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA Univ Calif San Diego La Jolla CA USA 92093 ch Med, La Jolla, CA 92093 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 3, anno: 2001,
pagine: 964 - 975
SICI:
1525-0016(200106)3:6<964:IOTPIR>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; VIVO PHAGE DISPLAY; ADENOASSOCIATED VIRUS; GENE-THERAPY; CANINE PARVOVIRUS; FUNCTIONAL IMPLICATIONS; BINDING PEPTIDES; TYPE-2 INFECTION; AAV VECTORS; HUMAN-CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Weitzman, MD Salk Inst Biol Studies, Genet Lab, POB 85800, San Diego, CA 92186 USA Salk Inst Biol Studies POB 85800 San Diego CA USA 92186 6 USA
Citazione:
M. Grifman et al., "Incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids", MOL THER, 3(6), 2001, pp. 964-975

Abstract

The human parvovirus adeno-associated virus type 2 (AAV-2) possesses many features that make it an attractive vector for gene delivery in vivo. However, its broad host range may limit its usefulness and effectivity in several gene therapy applications in which transgene expression needs to be limited to a specific organ or cell type. In this study, we explored the possibility of directing recombinant AAV-2 transduction by incorporating targetingpeptides previously isolated by in vivo phage display. Two putative loops within the AAV-2 capsid were examined as sites for incorporation of peptides. We tested the effects of deleting these loops and different strategies for the incorporation of several targeting peptides. The tumor-targeting sequence NGRAHA and a Myc epitope control were incorporated either as insertions or as replacements of the original capsid sequence. Viruses were assessed for packaging, accessibility of incorporated peptides, heparin binding, and transduction in a range of cell lines. Whereas recombinant viruses containing mutant capsid proteins were produced efficiently, transduction of several cell lines was significantly impaired for most modifications. However,certain mutants containing the peptide motif NCR, which binds CD13 (a receptor expressed in angiogenic vasculature and in many tumor cell lines), displayed an altered tropism toward cells expressing this receptor. Based on this work and previous studies, possible strategies for achieving in vivo targeting of recombinant AAV-2 are discussed.

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Documento generato il 22/01/20 alle ore 18:44:28