Journal ArticleDOI
Ex vivo gene transfer and correction for cell-based therapies
TLDR
This Review highlights the latest developments and the crucial challenges for cell-based therapies, with an emphasis on haematopoietic stem cell gene therapy, which is taken as a representative example given its advanced clinical translation.Abstract:
Cell-based therapies are fast-growing forms of personalized medicine that make use of the steady advances in stem cell manipulation and gene transfer technologies. In this Review, I highlight the latest developments and the crucial challenges for this field, with an emphasis on haematopoietic stem cell gene therapy, which is taken as a representative example given its advanced clinical translation. New technologies for gene correction and targeted integration promise to overcome some of the main hurdles that have long prevented progress in this field. As these approaches marry with our growing capacity for genetic reprogramming of mammalian cells, they may fulfil the promise of safe and effective therapies for currently untreatable diseases.read more
Citations
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Journal ArticleDOI
Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy.
Alessandra Biffi,Eugenio Montini,Laura Lorioli,Martina Cesani,Francesca Fumagalli,Tiziana Plati,Cristina Baldoli,Sabata Martino,Andrea Calabria,Sabrina Canale,Fabrizio Benedicenti,Giuliana Vallanti,Luca Biasco,Simone Leo,Nabil Kabbara,Gianluigi Zanetti,William B. Rizzo,Nalini Mehta,Maria Pia Cicalese,Miriam Casiraghi,Jaap Jan Boelens,Ubaldo Del Carro,David J. Dow,Manfred Schmidt,Andrea Assanelli,Victor Neduva,Clelia Di Serio,Elia Stupka,Jason P. Gardner,Christof von Kalle,Claudio Bordignon,Claudio Bordignon,Fabio Ciceri,Attilio Rovelli,Maria Grazia Roncarolo,Alessandro Aiuti,Maria Sessa,Luigi Naldini +37 more
TL;DR: The reconstitution of ARSA activity in the cerebrospinal fluid and the arrested progression of neurodegenerative disease in the three treated patients demonstrate that the transplanted cells, or their progeny, can seed the nervous system and deliver therapeutic levels of active enzyme.
Journal ArticleDOI
Gene therapy returns to centre stage
TL;DR: Technology for editing genes and correcting inherited mutations, the engagement of stem cells to regenerate tissues and the effective exploitation of powerful immune responses to fight cancer are also contributing to the revitalization of gene therapy.
Journal ArticleDOI
Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome
Alessandro Aiuti,Luca Biasco,Samantha Scaramuzza,Francesca Ferrua,Maria Pia Cicalese,Cristina Baricordi,Francesca Dionisio,Andrea Calabria,Stefania Giannelli,Maria Carmina Castiello,Marita Bosticardo,Costanza Evangelio,Andrea Assanelli,Miriam Casiraghi,Sara Di Nunzio,Luciano Callegaro,Claudia Benati,Paolo Rizzardi,Danilo Pellin,Clelia Di Serio,Manfred G. Schmidt,Christof von Kalle,Jason P. Gardner,Nalini Mehta,Victor Neduva,David J. Dow,Anne Galy,Roberto Miniero,Andrea Finocchi,Ayse Metin,Pinaki P. Banerjee,Jordan S. Orange,Stefania Galimberti,Maria Grazia Valsecchi,Alessandra Biffi,Eugenio Montini,Anna Villa,Fabio Ciceri,Maria Grazia Roncarolo,Luigi Naldini +39 more
TL;DR: A clinical protocol based on lentiviral vector (LV) gene transfer into autologous hematopoietic stem/progenitor cells (HSCs) resulted in robust, stable, and long-term engraftment of gene-corrected HSCs in the patients’ bone marrow, and the findings support the use of LV gene therapy to treat patients with WAS.
Journal ArticleDOI
Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges
TL;DR: The prospects and challenges for AAV gene therapy are to a large extent dependent on the target tissue and the specific disease.
Journal ArticleDOI
State-of-the-art gene-based therapies: the road ahead.
TL;DR: Improvements in the gene transfer vectors used in therapeutic trials have led to substantial clinical successes in patients with serious genetic conditions, such as immunodeficiency syndromes, blindness and some cancer types.
References
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Journal ArticleDOI
In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Luigi Naldini,Ulrike Blömer,Philippe Gallay,Daniel S. Ory,Richard C. Mulligan,Fred H. Gage,Inder M. Verma,Didier Trono +7 more
TL;DR: The ability of HIV-based viral vectors to deliver genes in vivo into nondividing cells could increase the applicability of retroviral vectors in human gene therapy.
Journal ArticleDOI
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Florent Ginhoux,Florent Ginhoux,Melanie Greter,Marylene Leboeuf,Sayan Nandi,Peter See,Solen Gokhan,Mark F. Mehler,Simon J. Conway,Lai Guan Ng,E. Richard Stanley,Igor M. Samokhvalov,Miriam Merad +12 more
TL;DR: Results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.
Journal ArticleDOI
The DNA Damage Response: Making It Safe to Play with Knives
TL;DR: This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.
Journal ArticleDOI
Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study.
Katarina Le Blanc,Francesco Frassoni,Lynne M. Ball,Franco Locatelli,Helene Roelofs,Ian D. Lewis,Edoardo Lanino,Berit Sundberg,Maria Ester Bernardo,Mats Remberger,Giorgio Dini,R. Maarten Egeler,Andrea Bacigalupo,Willem E. Fibbe,Olle Ringdén +14 more
TL;DR: Infusion of mesenchymal stem cells expanded in vitro, irrespective of the donor, might be an effective therapy for patients with steroid-resistant, acute GVHD.
Journal ArticleDOI
Hematopoietic Stem-Cell Transplantation
TL;DR: Hematopoietic stem-cell transplantation was first conceived more than 50 years ago, but problems associated with transplanting a nonsolid organ and modulating the immune response had to be solved before the procedure could be used clinically as mentioned in this paper.
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