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Titolo:
Modified adenovirus penton base protein (UTARVE) as a nonreplicating vector for delivery of antisense oligonucleotides with antiviral and/or antineoplastic activity
Autore:
Smith, CC; Kulka, M; Aurelian, L;
Indirizzi:
Univ Maryland, Sch Med, Virol Immunol Labs, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 t Therapeut, Baltimore, MD 21201 USA AuRx Inc, Baltimore, MD 21202 USA AuRx Inc Baltimore MD USA 21202AuRx Inc, Baltimore, MD 21202 USA
Titolo Testata:
INTERNATIONAL JOURNAL OF ONCOLOGY
fascicolo: 4, volume: 17, anno: 2000,
pagine: 841 - 850
SICI:
1019-6439(200010)17:4<841:MAPBP(>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
HERPES-SIMPLEX VIRUS; RIBONUCLEOTIDE REDUCTASE ICP10; EARLY MESSENGER RNA-4; LARGE SUBUNIT; KINASE-ACTIVITY; GENE-TRANSFER; INTEGRIN ALPHA-V-BETA-5; SIGNALING PATHWAYS; PK DOMAIN; TYPE-2;
Keywords:
adenovirus penton base protein; non-replicating vector; antiviral activity; antineoplastic activity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Aurelian, L Univ Maryland, Sch Med, Virol Immunol Labs, Dept Pharmacol & Expt Therapeut, 10 S Pine St, Baltimore, MD 21201 USA Univ Maryland 10 S Pine St Baltimore MD USA 21201 MD 21201 USA
Citazione:
C.C. Smith et al., "Modified adenovirus penton base protein (UTARVE) as a nonreplicating vector for delivery of antisense oligonucleotides with antiviral and/or antineoplastic activity", INT J ONCOL, 17(4), 2000, pp. 841-850

Abstract

Antisense oligonucleotides that selectively inhibit gene expression are a genetic approach for disease treatment and prevention. However, their use as therapeutic agents is complicated by their low rate of transport across cellular membranes and their sequestration within endocytic-like vesicles. We report that the adenovirus type-2 penton base protein modified to includethe fusogenic peptide of the influenza virus hemagglutinin protein is a non-replicating vector (designated UTARVE) that improves delivery of antisense oligonucleotides. Approximately 10-18% of the input vector was internalized by A549 and HeLa cells as determined by immunoblotting. It was cleared by proteolysis within 48 h. The vector had endosome disruptive potential as evidenced by erythrocyte lysis activity at low pH and a primarily diffuse cytoplasmic distribution in treated cells. Despite concentration and time-dependent cell detachment, UTARVE was not cytotoxic in the dye release assay. We used R1T1, an antisense oligonucleotide that inhibits expression of themultifunctional herpes simplex virus type-2 (HSV-2) R1 protein, HSV-2 growth and the proliferation of R1 PK transformed cells to examine vector-mediated delivery. Conjugated FITC-labeled R1T1 was rapidly (15-30 min) internalized by all cells treated at low (80 nM) concentration and the oligomer wasintracellularly dissociated from the vector. This compares to 65-83% of cells internalizing the unconjugated R1T1 when treated for 24 h. In antiviralassays, the IC50 and time required to inhibit HSV-2 growth were significantly lower for the conjugated (2 nM; 30 min) as compared to unconjugated (100 nM; 24 h) R1T1. The data indicate that the bioavailability and biologicalactivity of R1T1 were significantly increased by its delivery with UTARVE.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 10:14:47