Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy.

Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Abstract Text:

Haiyan Jiang,Linda B Couto,Susannah Patarroyo-White,Tongyao Liu,Dea Nagy,Joseph A Vargas,Shangzhen Zhou,Ciaran D Scallan,Jurg Sommer,Sharmila Vijay,Federico Mingozzi,Katherine A High,Glenn F Pierce,

In a clinical study of recombinant adeno-associated virus-2 expressing human factor IX (AAV2-FIX), we detected 2 impediments to long-term gene transfer. First, preexisting anti-AAV neutralizing antibodies (NABs) prevent vector from reaching the target tissue, and second, CD8(+) T-cell responses to hepatocyte-cell surface displayed AAV-capsid-terminated FIX expression after several weeks. Because the vector is incapable of synthesizing viral proteins, a short course of immunosuppression, until AAV capsid is cleared from the transduced cells, may mitigate the host T-cell response, allowing long-term expression of FIX. To evaluate coad-ministration of immunosuppression, we studied AAV8 vector infusion in rhesus macaques, natural hosts for AAV8. We administered AAV8-FIX in 16 macaques via the hepatic artery and assessed the effects of (1) preexisting anti-AAV8 NABs, (2) a standard T-cell immunosuppressive regimen, and (3) efficacy and safety of AAV8-FIX. We found that low titers (1:5) of preexisting NABs abrogate transduction, whereas animals with undetectable NABs are safely and effectively transduced by AAV8-FIX. Coadministration of mycophenolate mofetil and tacrolimus with vector does not induce toxicity and does not impair AAV transduction or FIX synthesis. These findings enable a clinical study to assess the effects of immunomodulation on long-term FIX expression in patients with hemophilia B.

Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Publishing Authors By Initials

H Jiang,LB Couto,S Patarroyo-White,T Liu,D Nagy,JA Vargas,S Zhou,CD Scallan,J Sommer,S Vijay,F Mingozzi,KA High,GF Pierce,

For similar organic chemicals: lactones: macrolides: tacrolimus research abstracts see: organic chemicals: lactones: macrolides: tacrolimus research

PUBMED ID PMID:

MEDLINE DATE:

Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Blood

VOLUME: 108

Page Numbers: 3321-8

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 25

MONTH: 07

YEAR: 2006

Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7603509

Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Keywords Mesh Terms:

KEYWORDS: Tacrolimus

MESH TERMS: administration & dosage

Chemical & Substance for Abstract: Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Information

Substance Name: Factor IX

Registry Number: 9001-28-9

Grant and Affiliation Information for Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy.

AFFILIATION: Bayer HealthCare Pharmaceuticals, 800 Dwight Way, Berkeley, CA 94710, USA. haiyan.jiang.b@bayer.com

Country: United States

AGENCY: United States NHLBI

GRANT: U01 HL66948

ACRONYM: HL

MEDLINETA: Blood

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy Related Publications

• A comparison of adenovirally delivered molecular methods to inhibit Na+/Ca2+ exchange.
• Analysis of a shield design for a DT neutron generator test facility.
• Automation usage decisions: controlling intent and appraisal errors in a target detection task.
• Book review.
• Characteristics of deaths occurring in hospitalised children: changing trends.
• Continuing education - "the action level"(r).
• Cooperative activation of D1-like and D2-like dopamine receptors in the nucleus accumbens shell is required for the reinstatement of cocaine-seeking behavior in the rat.
• Delivery and mechanistic considerations for the production of knock-in mice by single-stranded oligonucleotide gene targeting.
• Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions.
• Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy.
• Ethnic and racial disparities in diagnosis, treatment, and follow-up care.
• Linking sandeel consumption and the likelihood of starvation in harbour porpoises in the Scottish North Sea: could climate change mean more starving porpoises?
• Mass-dependent predation risk and lethal dolphin-porpoise interactions.
• Nicotinamide reduces acute cortical neuronal death and edema in the traumatically injured brain.
• Plasma and dietary carotenoids are associated with reduced oxidative stress in women previously treated for breast cancer.
• Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer.
• RanGAP-mediated nuclear protein import in vascular smooth muscle cells is augmented by lysophosphatidylcholine.
• Respiratory motion of the heart and positional reproducibility under active breathing control.
• Role of hypoxia in growth factor responses: differential effects of basic fibroblast growth factor and platelet-derived growth factor in an ischemic wound model.
• Role of platelet-derived growth factor in osteoblast function and bone synthesis.
• Short-term displacement and reproducibility of the breast and nodal targets under active breathing control.
• The drug use behaviour of cocaine users.
• The geography of diversification in mutualistic ants: a gene's-eye view into the Neogene history of Sundaland rain forests.
• The interactive effects of extended wakefulness and low-dose alcohol on simulated driving and vigilance.
• The pale child.
• The proteome of the mouse photoreceptor sensory cilium complex.
• Validation of the WHI brief physical activity questionnaire among women diagnosed with breast cancer.
• Wasste away: key elements of an integrated waste management program.
• Weight gain and recovery of pre-cancer weight after breast cancer treatments: evidence from the women's healthy eating and living (WHEL) study.
• When administered into the nucleus accumbens core or shell, the NMDA receptor antagonist AP-5 reinstates cocaine-seeking behavior in the rat.