Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Factors influencing the development of an anti-factor IX (FIX) response following administration of adeno-associated virus-FIX
Autore:
Ge, Y; Powell, S; Van Roey, M; McArthur, JG;
Indirizzi:
Cell Genesys, Dept Preclin Biol & Immunol, Foster City, CA 94404 USA Cell Genesys Foster City CA USA 94404 Immunol, Foster City, CA 94404 USA
Titolo Testata:
BLOOD
fascicolo: 12, volume: 97, anno: 2001,
pagine: 3733 - 3737
SICI:
0006-4971(20010615)97:12<3733:FITDOA>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT ADENOASSOCIATED VIRUS; COAGULATION FACTOR-IX; GENE-TRANSFER; HEMOPHILIA-B; IMMUNE-RESPONSES; VIRAL VECTORS; AAV VECTOR; EXPRESSION; TRANSGENE; TRANSDUCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
16
Recensione:
Indirizzi per estratti:
Indirizzo: McArthur, JG Cell Genesys, Dept Preclin Biol & Immunol, 342 Lakeside Dr, Foster City, CA 94404 USA Cell Genesys 342 Lakeside Dr Foster City CA USA 94404 404 USA
Citazione:
Y. Ge et al., "Factors influencing the development of an anti-factor IX (FIX) response following administration of adeno-associated virus-FIX", BLOOD, 97(12), 2001, pp. 3733-3737

Abstract

The present study sought to determine the impact of the route of administration of an adeno-associated virus (AAV) vector encoding human factor IX (hFIX) on the induction of an immune response against the vector and its xenogenic transgene product, hFIX, Increasing doses of AAV-hFIX were administered by different routes to C57BI/6 mice, which typically demonstrate significant immune tolerance to hFIX, The route of delivery had a profound impact on serum hFIX levels as well as the induction of an anti-hFIX humoral immune response. At all dose levels tested, delivery of AAV-hFIX by an intramuscular (IM) route induced an anti-body response against the human FIX proteinand no hFIX was detected in the serum of animals even at doses of 2 x 10(11) DNA viral particles (vp) of AAV-hFIX, This was in stark contrast to the mice that received AAV-hFIX by intraportal vein (IPV) administration. No anti-hFIX inhibitors were observed in any of these mice and therapeutic levels of hFIX were detected in the serum of all mice that received doses of 2 x10(10) vp AAV-hFIX and higher. When pre-existing neutralizing immunity to AAV was established in mice, AAV-hFIX administration by either the IM or IPV routes did not result in detectable serum hFIX. Although hFIX expression was not observed in mice with pre-existing neutralizing immunity to AAV, ananti-hFIX response was induced in all of the animals that received AAV-hFIX by the IM route. This was not observed in the preimmune mice that received AAV-hFIX by IPV administration. These results suggest that the threshold of inducing an immune response against a secreted transgene product, in this case the xenoprotein hFIX, is lower when the Vector is administered by the IM route even in animals with pre-existing immunity to AAV. (C) 2001 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/06/20 alle ore 10:18:05