Uncovering and dissecting the genotoxicity of self-inactivating lentiviral vectors in vivo.
Daniela Cesana,Marco Ranzani,Monica Volpin,Cynthia C. Bartholomae,C. Duros,A. Artus,Stefania Merella,Fabrizio Benedicenti,Lucia Sergi Sergi,Francesca Sanvito,Chiara Brombin,Alessandro Nonis,Clelia Di Serio,Claudio Doglioni,Christof von Kalle,Manfred Schmidt,Odile Cohen-Haguenauer,Luigi Naldini,Eugenio Montini +18 more
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TLDR
It is found that oncogene activation by promoter insertion is the most powerful mechanism of early vector-induced oncogenesis and this mechanism becomes predominant when the enhancer activity of the internal promoter is shielded by the presence of a synthetic chromatin insulator cassette.About:
This article is published in Molecular Therapy.The article was published on 2014-04-01 and is currently open access. It has received 142 citations till now. The article focuses on the topics: Insertional mutagenesis & Carcinogenesis.read more
Citations
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Clinical use of lentiviral vectors.
Michael C. Milone,Una O'Doherty +1 more
TL;DR: Three-generation, self-inactivating lentiviral vectors have recently been used in multiple clinical trials to introduce genes into hematopoietic stem cells to correct primary immunodeficiencies and hemoglobinopathies and long-term follow-up of patients treated with gene therapy products.
Journal ArticleDOI
Viral vector platforms within the gene therapy landscape
TL;DR: Viral vector-based gene therapy has seen a wave of drugs based on viral vectors that have gained regulatory approval that come in a variety of designs and purposes as discussed by the authors, such as vector based cancer therapies, to treating monogenic diseases with life-altering outcomes.
Journal ArticleDOI
Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned
TL;DR: The use of allogeneic hematopoietic stem cells to treat genetic blood cell diseases has become a clinical standard but is limited by the availability of suitable matched donors and potential immunologic complications, so gene therapy using autologous HSCs should be safer.
Journal ArticleDOI
Viral vectors for therapy of neurologic diseases.
Sourav Roy Choudhury,Eloise Hudry,Casey A. Maguire,Miguel Sena-Esteves,Xandra O. Breakefield,Paola Grandi +5 more
TL;DR: An overview of the current state and advances in the field of viral vector-mediated gene therapy for neurological disorders is provided, as well as preclinical and clinical progress made thus far for brain cancer and various neurodegenerative and neurometabolic disorders.
Journal ArticleDOI
Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the βA(T87Q)-Globin Gene
Olivier Negre,Anne-Virginie Eggimann,Yves Beuzard,Jean-Antoine Ribeil,Philippe Bourget,Suparerk Borwornpinyo,Suradej Hongeng,Salima Hacein-Bey,Marina Cavazzana,Philippe Leboulch,Emmanuel Payen,Emmanuel Payen +11 more
TL;DR: Proof-of-principle of efficacy and safety has already been obtained in multiple patients with β-thalassemia and sickle cell disease, and βAT87Q-globin is used both as a strong inhibitor of HbS polymerization and as a biomarker.
References
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BRAFE600-associated senescence-like cell cycle arrest of human naevi
Chrysiis Michaloglou,Liesbeth C.W. Vredeveld,Maria S. Soengas,Christophe Denoyelle,Thomas Kuilman,Chantal M.A.M. van der Horst,Donne Majoor,Jerry W. Shay,Wolter J. Mooi,Daniel S. Peeper +9 more
TL;DR: It is shown that sustained BRAFV600E expression in human melanocytes induces cell cycle arrest, which is accompanied by the induction of both p16INK4a and senescence-associated acidic β-galactosidase (SA-β-Gal) activity, a commonly usedsenescence marker.
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Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
Salima Hacein-Bey-Abina,Alexandrine Garrigue,Gary P. Wang,Jean Soulier,Annick Lim,Estelle Morillon,Emmanuelle Clappier,Laure Caccavelli,Eric Delabesse,Kheira Beldjord,Vahid Asnafi,Elizabeth Macintyre,Liliane Dal Cortivo,Isabelle Radford,Nicole Brousse,François Sigaux,Despina Moshous,Julia Hauer,Arndt Borkhardt,Bernd H. Belohradsky,Uwe Wintergerst,Maria C. Velez,Lily E. Leiva,Ricardo U. Sorensen,NM Wulffraat,Stéphane Blanche,Frederic D. Bushman,Alain Fischer,Marina Cavazzana-Calvo +28 more
TL;DR: These findings functionally specify a genetic network that controls growth in T cell progenitors and led to sustained remission in 3 of the 4 cases of T cell leukemia, but failed in the fourth.
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Cellular Senescence in Cancer and Aging
TL;DR: Cellular senescence, a state of irreversible growth arrest, can be triggered by multiple mechanisms including telomere shortening, the epigenetic derepression of the INK4a/ARF locus, and DNA damage, and together these mechanisms limit excessive or aberrant cellular proliferation.
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Pten is essential for embryonic development and tumour suppression.
TL;DR: The notion that PTEN haploinsufficiency plays a causal role in CD, LDD and BZS pathogenesis is supported, and it is demonstrated that Pten is a tumour suppressor essential for embryonic development.
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Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy
Nathalie Cartier,Salima Hacein-Bey-Abina,Cynthia C. Bartholomae,Gabor Istvan Veres,Manfred Schmidt,Ina Kutschera,Michel Vidaud,Ulrich Abel,Liliane Dal-Cortivo,Laure Caccavelli,Nizar Mahlaoui,Veronique Kiermer,Denice Mittelstaedt,Céline Bellesme,Najiba Lahlou,François Lefrère,Stéphane Blanche,Muriel Audit,Emmanuel Payen,Philippe Leboulch,Philippe Leboulch,Bruno l’Homme,Pierre Bougnères,Christof von Kalle,Alain Fischer,Marina Cavazzana-Calvo,Patrick Aubourg +26 more
TL;DR: Lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD, and progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT.
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