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Titolo:
Ablating adenovirus type 5 fiber-CAR binding and HI loop insertion of the SIGYPLP peptide generate an endothelial cell-selective adenovirus
Autore:
Nicklin, SA; Von Seggern, DJ; Work, LM; Pek, DCK; Dominiczak, AF; Nemerow, GR; Baker, AH;
Indirizzi:
Univ Glasgow, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland UnivGlasgow Glasgow Lanark Scotland G11 6NT ow G11 6NT, Lanark, Scotland Scripps Clin & Res Inst, Dept Immunol, La Jolla, CA 92037 USA Scripps Clin& Res Inst La Jolla CA USA 92037 nol, La Jolla, CA 92037 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 4, anno: 2001,
pagine: 534 - 542
SICI:
1525-0016(200112)4:6<534:AAT5FB>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
VIVO PHAGE DISPLAY; IN-VIVO; VASCULAR ENDOTHELIUM; RECEPTOR; DELIVERY; VECTOR; PROTEIN; TROPISM; ANTIBODIES; MECHANISM;
Keywords:
adenovirus; targeting; phage display; HI loop; CAR ablation; peptides; endothelial cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Baker, AH Univ Glasgow, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G11 6NT , Lanark, Scotland
Citazione:
S.A. Nicklin et al., "Ablating adenovirus type 5 fiber-CAR binding and HI loop insertion of the SIGYPLP peptide generate an endothelial cell-selective adenovirus", MOL THER, 4(6), 2001, pp. 534-542

Abstract

Adenovirus type 5 (Ad) based vectors transduce vascular endothelial cells (EC) and have been widely used for vascular gene transfer. However, many cell types express the Ad receptor (coxsackievirus adenovirus receptor; CAR),preventing selective EC infection and precluding clinical use. We previously isolated the human EC-binding peptides SIGYPLP and LSNFHSS by phage display and demonstrated by means of a bispecific antibody that SIGYPLP directsefficient, high-level, EC-selective Ad-mediated gene transfer. We now generate genetically modified Ad fiber proteins with selective EC tropism by engineering these peptides into the HI loop of the Ad fiber. SIGYPLP, but notLSNFHSS, enhanced EC selectivity, demonstrating maintenance of peptide-cell binding fidelity upon incorporation into virions. Combining fiber mutations that block CAR binding (detargeting) with SIGYPLP insertion (retargeting) generated a novel Ad vector, AdKO1SIG, in a single component system. AdKO1SIG demonstrated efficient and selective tropism for EC compared with control Ad vectors. This is the first demonstration of genetic incorporation ofa novel, mammalian, cell-selective ligand that retains its targeting fidelity in the Ad fiber HI loop, in combination with point mutations that abolish fiber-CAR interaction. This study demonstrates the potential for improving the cell-selectivity and safety of adenoviral vectors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/21 alle ore 18:21:08