Comprehensive genomic access to vector integration in clinical gene therapy

被引：0

作者：

Richard Gabriel

Ralph Eckenberg

Anna Paruzynski

Cynthia C Bartholomae

Ali Nowrouzi

Anne Arens

Steven J Howe

Alessandra Recchia

Claudia Cattoglio

Wei Wang

Katrin Faber

Kerstin Schwarzwaelder

Romy Kirsten

Annette Deichmann

Claudia R Ball

Kamaljit S Balaggan

Rafael J Yáñez-Muñoz

Robin R Ali

H Bobby Gaspar

Luca Biasco

Alessandro Aiuti

Daniela Cesana

Eugenio Montini

Luigi Naldini

Odile Cohen-Haguenauer

Fulvio Mavilio

Adrian J Thrasher

Hanno Glimm

Christof von Kalle

William Saurin

Manfred Schmidt

机构：

[1] National Center for Tumor Diseases and German Cancer Research Center,Department of Translational Oncology

[2] Genomining,Department of Biomedical Sciences

[3] Genomics and Proteomics Core Facilities,Department of Clinical Immunology

[4] German Cancer Research Center,Department of Public Health and Cell Biology

[5] Molecular Immunology Unit,Department of Clinical Oncology

[6] Institute of Child Health,undefined

[7] University College,undefined

[8] University of Modena and Reggio Emilia,undefined

[9] Cancer Immunotherapy and Gene Therapy Program,undefined

[10] Instituto Scientifico H. San Raffaele,undefined

[11] Institute of Ophthalmology,undefined

[12] University College London,undefined

[13] School of Biological Sciences,undefined

[14] Royal Holloway–University of London,undefined

[15] Great Ormond Street Hospital NHS Trust,undefined

[16] San Raffaele Telethon Institute for Gene Therapy,undefined

[17] University of Rome Tor Vergata,undefined

[18] Laboratoire de Biotechnologie et Pharmacologie Génétique Appliquées,undefined

[19] Ecole Normale Supérieure de Cachan,undefined

[20] Oncogenetics,undefined

[21] Hôpital Saint-Louis,undefined

[22] Molecular and Gene Therapy Program,undefined

[23] Cincinnati Children's Research Foundation,undefined

来源：

Nature Medicine | 2009年 / 15卷

关键词：

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Adverse events stemming from the use of retroviral vectors in humans has prompted the search for methods predicting the fate and biological consequences of gene-modified cells after vector insertion. Methods of integration site analysis, such as linear amplification-mediated PCR (LAM-PCR), rely on use of restriction enzymes and identify only a fraction of all genomic integrants. This report describes a non–restriction enzyme–based LAM-PCR technique that provides comprehensive, unbiased integration site analysis.

引用

页码：1431 / 1436

页数：5

共 35 条

[1] Aiuti A(2002)Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning Science 296 2410-2413
[2] Cavazzana-Calvo M(2000)Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease Science 288 669-672
[3] Flotte TR(2007)Gene therapy: the first two decades and the current state-of-the-art J. Cell. Physiol. 213 301-305
[4] Gaspar HB(2004)Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector Lancet 364 2181-2187
[5] Hacein-Bey-Abina S(2003)LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1 Science 302 415-419
[6] Howe S(2008)Insertional mutagenesis in combination with acquired somatic mutations leads to leukemogenesis following gene therapy of SCID-X1 J. Clin. Invest. 118 3143-3150
[7] Ott MG(2006)Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1 Nat. Med. 12 401-409
[8] Aiuti A(2007)Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy J. Clin. Invest. 117 2233-2240
[9] Bohne J(2008)Genotoxicity in gene therapy: An account of vector integration and designer nucleases Curr. Opin. Mol. Ther. 10 214-223
[10] Cathomen T(2007)Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy J. Clin. Invest. 117 2225-2232

← 1 2 3 4 →