Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults.

Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Research Abstract Details 

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Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Abstract Text:

Mark L Brantly,L Terry Spencer,Margaret Humphries,Thomas J Conlon,Carolyn T Spencer,Amy Poirier,Wendy Garlington,Dawn Baker,Sihong Song,Kenneth I Berns,Nicholas Muzyczka,Richard O Snyder,Barry J Byrne,Terence R Flotte,

A phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 (rAAV2) alpha1-antitrypsin (AAT) vector was performed in 12 AAT-deficient adults, 10 of whom were male. All subjects were either homozygous for the most common AAT mutation (a missense mutation designated PI*Z) or compound heterozygous for PI*Z and another mutation known to cause disease. There were four dose cohorts, ranging from 2.1 x 10(12) vector genomes (VG) to 6.9 x 10(13) VG, with three subjects per cohort. Subjects were injected sequentially in a dose-escalating fashion with a minimum of 14 days between patients. Subjects who had been receiving AAT protein replacement discontinued that therapy 28 days before vector administration. There were no vector-related serious adverse events in any of the 12 participants. Vector DNA sequences were detected in the blood between 1 and 3 days after injection in nearly all patients receiving doses of 6.9 x 10(12) VG or higher. Anti-AAV2 capsid antibodies were present and rose after vector injection, but no other immune responses were detected. One subject who had not been receiving protein replacement exhibited low-level expression of wild-type M-AAT in the serum (82 nM), which was detectable 30 days after receiving an injection of 2.1 x 10(13) VG. Unfortunately, residual but declining M-AAT levels from the washout of the protein replacement elevated background levels sufficiently to obscure any possible vector expression in that range in most of the other individuals in the higher dose cohorts.

Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Publishing Authors By Initials

ML Brantly,LT Spencer,M Humphries,TJ Conlon,CT Spencer,A Poirier,W Garlington,D Baker,S Song,KI Berns,N Muzyczka,RO Snyder,BJ Byrne,TR Flotte,

For similar skin and connective tissue diseases: connective tissue diseases: alpha 1-antitrypsin deficiency research abstracts see: skin and connective tissue diseases: connective tissue diseases: alpha 1-antitrypsin deficiency research

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Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Journal Published:

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

Journal: Human gene therapy

VOLUME: 17

Page Numbers: 1177-86

Journal Abbreviation:

ISSN: 1043-0342

DAY: 3

MONTH: Dec

YEAR: 2006

Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9008950

Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Keywords Mesh Terms:

KEYWORDS: alpha 1-Antitrypsin Deficiency

MESH TERMS: therapy

Chemical & Substance for Abstract: Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Information

Substance Name: alpha 1-Antitrypsin

Registry Number: 0

Grant and Affiliation Information for Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults.

AFFILIATION: Department of Medicine, University of Florida, Gainesville, FL 32611, USA.

Country: United States

AGENCY: United States NCRR

GRANT: RR00082

ACRONYM: RR

MEDLINETA: Hum Gene Ther

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