Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins.
Amit C. Nathwani,Amit C. Nathwani,Cecilia Rosales,Jenny McIntosh,Ghasem Rastegarlari,Devhrut Nathwani,Deepak Raj,Sushmita Nawathe,Simon N. Waddington,Roderick T. Bronson,Scott Jackson,Robert E. Donahue,Katherine A. High,Federico Mingozzi,Catherine Y.C. Ng,Junfang Zhou,Yunyu Spence,M. Beth McCarville,Marc Valentine,James A. Allay,John Coleman,Susan Sleep,John T. Gray,Arthur W. Nienhuis,Andrew M. Davidoff +24 more
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TLDR
The long-term consequences of a single intravenous administration of a self-complementary AAV vector encoding a codon optimized human factor IX gene in 24 nonhuman primates revealed no toxicity, and data support further evaluation of this vector in hemophilia B patients.About:
This article is published in Molecular Therapy.The article was published on 2011-05-01 and is currently open access. It has received 284 citations till now.read more
Citations
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Journal ArticleDOI
Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B
Amit C. Nathwani,Edward G. D. Tuddenham,Savita Rangarajan,Cecilia Rosales,Jenny McIntosh,David C. Linch,Pratima Chowdary,Anne Riddell,Arnulfo Jaquilmac Pie,Chris Harrington,James O'Beirne,Keith Smith,John Pasi,Bertil Glader,Pradip Rustagi,Catherine Y.C. Ng,Mark A. Kay,Junfang Zhou,Yunyu Spence,Christopher L. Morton,James A. Allay,John Coleman,Susan Sleep,John M. Cunningham,Deokumar Srivastava,Etiena Basner-Tschakarjan,Federico Mingozzi,Katherine A. High,John T. Gray,Ulrike M. Reiss,Arthur W. Nienhuis,Andrew M. Davidoff +31 more
TL;DR: Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects.
Journal ArticleDOI
Long-term safety and efficacy of factor IX gene therapy in hemophilia B
Amit C. Nathwani,Ulreke M Reiss,Edward G. D. Tuddenham,Cecilia Rosales,Cecilia Rosales,Pratima Chowdary,Jenny McIntosh,Marco Della Peruta,Elsa Lheriteau,Nishal Patel,Deepak Raj,Deepak Raj,Anne Riddell,Jun Pie,Savita Rangarajan,Savita Rangarajan,David H. Bevan,Michael Recht,Yu-min P Shen,Kathleen Halka,Etiena Basner-Tschakarjan,Federico Mingozzi,Katherine A. High,James A. Allay,Mark A. Kay,Catherine Y.C. Ng,Junfang Zhou,Maria I Cancio,Christopher L. Morton,John T. Gray,Deo Kumar Srivastava,Arthur W. Nienhuis,Andrew M. Davidoff +32 more
TL;DR: In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement, and with a follow-up period of up to 3 years, no late toxic effects from the therapy were reported.
Journal ArticleDOI
Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain
Benjamin E. Deverman,Piers L. Pravdo,Bryan P. Simpson,Sripriya Ravindra Kumar,Ken Y. Chan,Abhik Banerjee,Wei Li Wu,Bin Yang,Nina Huber,Sergiu P. Paşca,Viviana Gradinaru +10 more
TL;DR: This work uses Cre recombination–based AAV targeted evolution (CREATE) to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection and demonstrates the potential of CREATE to produce customized AAV vectors for biomedical applications.
Journal ArticleDOI
Prevention of muscular dystrophy in mice by CRISPR/Cas9–mediated editing of germline DNA
Chengzu Long,John R. McAnally,John M. Shelton,Alex A. Mireault,Rhonda Bassel-Duby,Eric N. Olson +5 more
TL;DR: A mutation that causes muscular dystrophy in mice can be corrected by genome editing, which prevents the disease from developing, and this proof of concept sets the stage for applying genome editing to specific cell types involved in the disease.
Journal ArticleDOI
Emerging Issues in AAV-Mediated In Vivo Gene Therapy
TL;DR: The liver will be used as a model target tissue for gene transfer based on the large amount of data available from preclinical and clinical studies, and key achievements and emerging issues in the field are presented.
References
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Journal ArticleDOI
Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response
Catherine S. Manno,Glenn F. Pierce,Valder R. Arruda,Bertil Glader,Margaret V. Ragni,Rasko Jj,Margareth C. Ozelo,Keith Hoots,Blatt P,Barbara A. Konkle,Michael D. Dake,Robin D. Kaye,Mahmood K. Razavi,A Zajko,James L. Zehnder,Pradip Rustagi,Hiroyuki Nakai,A Chew,Debra G.B. Leonard,Debra G.B. Leonard,J F Wright,Ruth Lessard,Jurg M. Sommer,Michael Tigges,Denise E. Sabatino,A Luk,Haiyan Jiang,Federico Mingozzi,Linda B. Couto,Hildegund C.J. Ertl,Katherine A. High,Katherine A. High,Mark A. Kay +32 more
TL;DR: In this article, a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B.
Journal ArticleDOI
Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy
TL;DR: Vectors based on AAV7 and AAV8 should be considered for human gene therapy because of low reactivity to antibodies directed to human AAVs and because gene transfer efficiency in muscle was similar to that obtained with the best known serotype, whereas, in liver, gene transfer was substantially higher than previously described.
Journal ArticleDOI
Repeat-induced gene silencing in mammals.
TL;DR: Use of the loxCre system of site-specific recombination is described to generate transgenic mouse lines in which different numbers of a transgene are present at the same chromosomal location, thereby eliminating the contribution of position effects and allowing analysis of the effect of copy number alone on transGene silencing.
Journal ArticleDOI
AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B.
Catherine S. Manno,Amy J. Chew,Sylvia Hutchison,Peter J. Larson,Roland W. Herzog,Valder R. Arruda,Shing Jen Tai,Margaret V. Ragni,Arthur A. Thompson,Margareth C. Ozelo,Linda B. Couto,Debra G.B. Leonard,Fred Johnson,Alan McClelland,Ciaran Scallan,Erik D. Skarsgard,Alan W. Flake,Mark A. Kay,Katherine A. High,Bertil Glader +19 more
TL;DR: Results of the first parenteral administration of rAAV demonstrate that administration of AAV vector by the intramuscular route is safe at the doses tested and effects gene transfer and expression in humans in a manner similar to that seen in animals.
Journal ArticleDOI
AAV Vector Integration Sites in Mouse Hepatocellular Carcinoma
Anthony Donsante,Daniel G. Miller,Yi Li,Carole Vogler,Elizabeth M. Brunt,David W. Russell,Mark S. Sands +6 more
TL;DR: It is shown that normal mice and mice with mucopolysaccharidosis VII (MPS VII) develop hepatocellular carcinoma (HCC) after neonatal injection of an AAV vector expressing b-glucuronidase, which implicate this locus in the development of HCC and raise concerns over the clinical use of AAV vectors.
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Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response
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Long-term safety and efficacy of factor IX gene therapy in hemophilia B
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