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Titolo:
Sustained and complete phenotype correction of hemophilia B mice followingintramuscular injection of AAV1 serotype vectors
Autore:
Chao, HJ; Monahan, PE; Liu, YB; Samulski, RJ; Walsh, CE;
Indirizzi:
Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 y Ctr, Chapel Hill, NC 27599 USA Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 ediat, Chapel Hill, NC 27599 USA Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 t Med, Chapel Hill, NC 27599 USA Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 macol, Chapel Hill, NC 27599 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 3, volume: 4, anno: 2001,
pagine: 217 - 222
SICI:
1525-0016(200109)4:3<217:SACPCO>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
COAGULATION-FACTOR-IX; RECOMBINANT ADENOASSOCIATED VIRUS; GENE-TRANSFER; FACTOR-VIII; EXPRESSION; CANINE; PERSISTENT; INDUCTION; RESPONSES; ANTIGENS;
Keywords:
adeno-associated virus; serotype; hemophilia B; mutant mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Walsh, CE Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 pel Hill, NC 27599 USA
Citazione:
H.J. Chao et al., "Sustained and complete phenotype correction of hemophilia B mice followingintramuscular injection of AAV1 serotype vectors", MOL THER, 4(3), 2001, pp. 217-222

Abstract

We previously reported that direct intramuscular injection of non-serotype-2 AAV vectors, especially AAV serotype 1 (AAV1), resulted in expression ofsupranormal levels of canine F9 in immunodeficient mice. Here we test the ability of the AAV1-F9 vector to deliver sustained expression and correction of factor IX (FIX) deficiency in genetically engineered hemophilic mice. Intramuscular injection of AAV1-F9 resulted in 100-1000 times more canine F9 in plasma of recombinant AAV1-F9 mice compared with injection of AAV2-F9. Assessment of clotting activity by activated partial thromboplastin time confirmed that circulating canine FIX was indeed functional. Moreover, phenotypic correction assayed by tail clip challenge resulted in survival of allAAV1-F9 treated animals, in contrast to naive mice and 50 % of AAV2-treated hemophilia B mice, which failed to survive. Administration of cyclophosphamide (CTX) was required to suppress formation of anti-canine FIX antibodies for AAV2-treated animals, whereas it was dispensable for those treated with AAV1-F9. This difference in immunogenicity further emphasizes the usefulness of serotype-specific vectors. Finally, we report that correction of the hemophilia phenotype using AAV1-F9 was complete and persistent (over 8 months), a result that underscores the value of continued exploration of alternative AAV serotype vectors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/02/20 alle ore 00:51:19