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Mol Ther. Feb 2013; 21(2): 266–268.
Published online Feb 1, 2013. doi:  10.1038/mt.2013.4
PMCID: PMC3594019
Translating the Genomics Revolution: The Need for an International Gene Therapy Consortium for Monogenic Diseases
Jacques P Tremblay,1* Xiao Xiao,2 Annemieke Aartsma-Rus,3 Carlos Barbas,4 Helen M Blau,5 Adam J Bogdanove,6 Kym Boycott,7 Serge Braun,8 Xandra O Breakefield,9 Juan A Bueren,10 Michael Buschmann,11 Barry J Byrne,12 Michele Calos,13 Toni Cathomen,14 Jeffrey Chamberlain,15 Marinee Chuah,16 Kenneth Cornetta,17 Kay E Davies,18 J George Dickson,19 Philippe Duchateau,20 Terence R Flotte,21 Daniel Gaudet,22 Charles A Gersbach,23 Renald Gilbert,24 Joseph Glorioso,25 Roland W Herzog,26 Katherine A High,27 Wenlin Huang,28 Johnny Huard,29 J Keith Joung,30 Depei Liu,31 Dexi Liu,32 Hanns Lochmüller,33 Lawrence Lustig,34 Jeffrey Martens,35 Bernard Massie,36 Fulvio Mavilio,37 Jerry R Mendell,38 Amit Nathwani,39 Katherine Ponder,40 Matthew Porteus,41 Jack Puymirat,42 Jude Samulski,43 Shin'ichi Takeda,44 Adrian Thrasher,45 Thierry VandenDriessche,46 Yuquan Wei,47 James M Wilson,48 Steve D Wilton,49 John H Wolfe,50 and Guangping Gao51
1Centre de Recherche du CHU and Department of Molecular Medicine, Université Laval, Quebec, Quebec, Canada
2University of North Carolina School of Pharmacy, Chapel Hill, North Carolina, USA
3Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
4The Skaggs Institute for Chemical Biology and the Departments of Molecular Biology and Chemistry, The Scripps Research Institute, La Jolla, California, USA
5Baxter Laboratory for Stem Cell Biology, Stanford University School of Medicine, Stanford, California, USA
6Department of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, New York, USA
7Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada
8AFM Telethon, Paris, France
9Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, Massachusetts, USA
10Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas and Centro de Investigación en Red de Enfermedades Raras (CIEMAT/CIBERER), Madrid, Spain
11Department of Chemical Engineering and Institute of Biomedical Engineering, Ecole Polytechnique, Montreal, Quebec, Canada
12Department of Pediatrics, University of Florida, Gainesville, Florida, USA
13Department of Genetics, Stanford University School of Medicine, Stanford, California, USA
14Laboratory of Cell and Gene Therapy, Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany
15Departments of Neurology, Medicine, and Biochemistry, University of Washington School of Medicine, Seattle, Washington, USA
16Department of Gene Therapy and Regenerative Medicine, Vrije Universiteit Brussel and Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
17Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA
18MRC Functional Genomics Unit, University of Oxford, Oxford, UK
19School of Biological Sciences, Royal Holloway–University of London, Egham, Surrey, UK
20Cellectis, Paris, France
21Gene Therapy Center and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA
22Department of Medicine, Université de Montréal, Montreal, Quebec, Canada
23Department of Biomedical Engineering and Institute for Genome Science and Policy, Duke University, Durham, North Carolina, USA
24Biotechnology Research Institute, Montreal, Quebec, Canada
25Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
26Department of Pediatrics, University of Florida, Florida, USA
27Perelman School of Medicine at the University of Pennsylvania and Howard Hughes Medical Institute at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
28State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China
29Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
30Molecular Pathology Unit, Massachusetts General Hospital, Charlestown and Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
31Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
32Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, Georgia, USA
33Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, UK
34Department of Otolaryngology–Head and Neck Surgery, University of California, San Francisco, San Francisco, California, USA
35Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA
36Biotechnology Research Institute, Montreal, Quebec, Canada
37Genethon, Evry, France
38Paul D. Wellstone Center, Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio, USA
39Department of Haematology, UCL Cancer Institute, London, UK
40Department of Internal Medicine, Washington University, St Louis, Missouri, USA
41Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA
42Centre de Recherche du CHU and Department of Molecular Medicine, Université Laval, Quebec, Quebec, Canada
43Cardiothoracic Division, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
44National Center of Neurology and Psychiatry, Tokyo, Japan
45UCL Institute of Child Health, London, UK
46Department of Gene Therapy and Regenerative Medicine, Vrije Universiteit Brussel and Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
47National Gene Therapy Program, National Key Laboratory of Biotherapy, and Sichuan University, Chengdu, China
48Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
49Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Crawley, Australia
50University of Pennsylvania and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
51University of Massachusetts Medical School, Worcester, MA, USA
To the editor:
Over the past decade, gene therapy has been successfully used to treat several monogenic disorders, and it shows promise for treating diseases of more complex etiology. In addition, the recent development of induced pluripotent stem cells now opens the possibility of transplanting genetically corrected autologous cells.1,2 Very recently, the European Medicines Agency approved the first gene therapy treatment in the Western world.3 The substantial progress over the preceding decades arguably portends the development of gene therapies for most monogenic diseases. Given this remarkable opportunity, we are proposing the creation of an International Gene Therapy Consortium for Monogenic Diseases. This consortium would facilitate coordination of the production and availability of a variety of vectors, oligonucleotides, and recombinant proteins—including zinc-finger nucleases and Tal effector nucleases—as well as support the development of suitable animal models, preclinical studies, and clinical trials. Financial resources should be developed so as to attract collaborations from the private sector to boost the development of a gene therapy industry, similar to the way the Apollo project to explore the moon stimulated growth of the space and computer industries in the 1960s. In this century, a similar concerted effort will be required to develop effective treatments and even cures of diseases here on Earth!
A model for such a consortium can be found in the field of genomics. Advances in genomics have been rapid, owing in large part to the formation of international consortia such as the Human Genome and the ENCODE (Encyclopedia of DNA Elements) projects. These consortia have been awarded large budgets by various government agencies that have permitted intense collaboration among scientists as well as engagement of industry for the development of supporting technologies. The funding made available for these projects contrasts sharply with the relatively limited budgets that have been available for gene therapy research. Typically, most gene therapy researchers work as small teams on a specific disease with a relatively small budget. Moreover, the funding for gene therapy research tends to be piecemeal, with part coming from private foundations supported by patients, parents, and friends. Although these small groups can provide proof of concept for a gene therapy approach in cell and animal models, they generally lack the expertise and funding to efficiently translate their strategies to a clinical trial.
The fragmentation of gene therapy research efforts and the limited funding thus present significant hurdles for clinical translation. The establishment of an international gene therapy consortium would allow these small groups to tap into broader expertise and infrastructure, increasing the likelihood of a potentially beneficial treatment moving to clinical trials. There are already smaller consortia that can serve as examples. Indeed, European Union–sponsored collaborative networks in Europe have demonstrated the advantages of consortia-fostered collaboration among basic scientists, clinical investigators, industry, patient organizations and regulatory authorities. This format of collaboration and interactive multidisciplinary networks is ideally suited to address the various challenges of this multifaceted field. Consequently, such a concerted effort is much more cost-effective. One such group, the Transatlantic Gene Therapy Consortium, has successfully developed gene therapy strategies and trials predominantly for rare hematologic and immunologic diseases. In the EU Seventh Framework Programme, two pan-European translational projects have been funded, one focusing on neuro­logical and neurodegenerative diseases (NEUROMICS), the other on rare diseases of the kidney (EuRenOmics). In the United States, the Rare Diseases Clinical Research Network was funded by the National Institutes of Health and the Office for Rare Diseases Research in order to facilitate collaboration among experts in many types of rare diseases. The FORGE Canada project, a national consortium of clinicians and scientists, is using next-generation sequencing technology to identify genes responsible for 200 rare pediatric-onset disorders and investigate their molecular etiology. The International Rare Diseases Research Consortium (IRDiRC), launched in April 2011, aims to foster international collaboration, maximizing resources and coordinating efforts in rare-diseases research. Worldwide sharing of information, data, and samples is currently hampered by the absence of an exhaustive rare-disease classification, standard terms of reference, common ontologies, and harmonized regulatory requirements. The IRDiRC has two main objectives to achieve by the year 2020: to deliver 200 new therapies for rare diseases and the means to diagnose most rare diseases. The group will next develop the scientific and policy framework to guide research activities and foster collaboration among the stakeholders to systematically explore the opportunities to accelerate the development of diagnostics and therapies for rare diseases. However, it should be emphasized that currently the majority of the 200 therapies sought by this consortium are based on the use of small molecules rather than on gene and/or cell therapy.
We believe that there is a need for a larger gene therapy consortium, with a larger budget, to focus on developing definitive gene and cell therapy treatments for most monogenic hereditary diseases over the next 20 years. This consortium will permit the development of focused areas of expertise. A major impediment to the commercialization of gene therapy for rare diseases lies in the lack of a sound business model for companies owing to the small number of patients, the fact that a single treatment can cure a patient for life, and the requirements for long-term evaluation by federal agencies. As recently suggested, public funds could be used to pay for centralized manufacturing facilities and to subsidize enterprises with the necessary expertise, as has been done for vaccines.4 A worldwide consortium would also facilitate the assembly of larger cohorts of patients with specific rare diseases, which are present in very small numbers in individual countries; this would allow for more robust clinical trial designs. Finally, a gene therapy consortium could facilitate long-term evaluation of integration sites and adverse events so as to better track the safety of new therapies. The creation of an International Gene Therapy Consortium for Monogenic Diseases would thus be, for these diseases, the first concrete step toward the personalized medicine that genomic research makes possible. It should be emphasized that some of these diseases (e.g., sickle cell disease and γ-thalassemia) affect millions of peoples.
Like mankind's quest to travel to the moon in the 1960s, this proposal represents a grand challenge, but we have a societal obligation to the rare-disease community to collaborate and build the infrastructure to meet it. With an international consortium in place, it is more likely that therapies will be established that help patients not only in the developed world but also in less developed parts of our planet. Importantly, current scientific developments make this a timely challenge, and, in the long term, gene therapies for these diseases should become cost-effective. Just as we witnessed with the Human Genome Project, the technologies to correct the human genome will progress over the years with the appropriate incentives, generating a boost for the new knowledge-based economy. The time to take this step is now.
The scientists and directors of foundations or patient associations that would like to support the creation of such a consortium are invited to e-mail Jacques P. Tremblay at
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  • Gaudet D, Méthot J, Déry S, Brisson D, Essiembre C, Tremblay G. et al. (2012. Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPL(S447X)) gene therapy for lipoprotein lipase deficiency: an open-label trial Gene Ther, e-pub ahead of print 21 June 2012 . [PubMed]
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Articles from Molecular Therapy are provided here courtesy of
The American Society of Gene & Cell Therapy