A Comeback for Gene Therapy

  title={A Comeback for Gene Therapy},
  author={Luigi Naldini},
  pages={805 - 806}
  • L. Naldini
  • Published 6 November 2009
  • Medicine, Biology
  • Science
A lentivirus was used as a vector in hemato-poietic stem cells to treat a neurodegenerative disease in a clinical gene therapy trial. Gene therapy has recently had some important successes in treating severe inherited diseases (1–3) after years of skepticism from the scientific community and neglect by the pharmaceutical industry. On page 818 in this issue, Cartier et al. (4) report another major advance—the successful first clinical testing of an HIV-derived vector in hematopoietic stem cell… 

Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy

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.

Gene therapy research in Asia

This review aims to highlight recent progress in gene therapy clinical trials and discuss the prospects for the future in China and wider Asia.

Development of a Liver Gene Therapy Strategy for Haemophilia B With Lentiviral Vectors

Evidence is provided that liver gene therapy can establish long-term FIX expression and immune tolerance in mice even in the presence of pre-existing anti-FIX antibody immunity, and integrase-defective LVs may represent a valuable strategy to induce stable antigen-specific tolerance by transient gene transfer and offer a treatment for immune-mediated diseases.

[Gene therapy: a therapeutic option for neoplasias, infections and monogenic diseases].

The objective of this article is to comment the way gene therapy addresses nowadays the treatment of such different pathologies as neoplasias, infections and monogenic diseases.

Combining stem cells and genes for effective therapeutics.

The opportunities and challenges of combining gene- and stem cell-therapy, and the potential comeback of gene therapy, are discussed.

Preclinical and clinical progress in hemophilia gene therapy

New insights from clinical trials and advances in preclinical studies may ultimately pave the way toward a cure in patients suffering from hemophilia.

Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders

Recently, the clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 gene-editing tool has taken a center stage in gene therapy research and is reported to be efficient and highly precise.

Clinical development of gene therapy: results and lessons from recent successes

positive outcomes have been documented for a wide range of genetic diseases (including hematological, immunological, ocular, and neurodegenerative and metabolic disorders) and several types of cancer and many more are in the pipeline.

Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency

In comparison with SCID-X1, ADA-SCID gene therapy presents a better safety profile and engraftment of multilineage transduced stem/progenitor cells, thanks to the use of nonmyeloablative preconditioning.

A single epidermal stem cell strategy for safe ex vivo gene therapy

A clonal strategy is a powerful and efficient means of by‐passing the heterogeneity of a transduced stem cell population and makes it possible to envision exciting gene‐editing technologies like zinc finger nucleases, TALENs and homologous recombination for next‐generation gene therapy.



Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy

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.

Gene therapy for immunodeficiency due to adenosine deaminase deficiency.

Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency and effective protection against infections and improvement in physical development made a normal lifestyle possible.

In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector

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.

Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors.

A lentiviral vector was able to transduce human CD34+ cells capable of stable, long-term reconstitution of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice and resulted in transgene expression in multiple lineages of human hematopoietic cells for up to 22 weeks after transplantation.

Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1

The results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD.

The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy.

It is determined that substantially greater LV integration loads are required to approach the same oncogenic risk as gammaRVs, which strongly support the use of SIN viral vector platforms and show that ISS can substantially modulate genotoxicity.

Efficient transduction of pigtailed macaque hematopoietic repopulating cells with HIV-based lentiviral vectors.

The data suggest that lentiviral vectors should be highly effective for HSC gene therapy, particularly for diseases in which maintaining the engraftment potential of stem cells using short-term ex vivo transduction protocols is critical.

Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors.

Reports addressing what extent the outcome of insertional mutagenesis induced by gene vectors is related to the architecture and type of vector used, intrinsic properties of the target cell, and extrinsic and potentially disease-specific factors influencing clonal competition in vivo are discussed.

Preliminary results of gene therapy for retinal degeneration.

The first results of separate clinical trials investigating the short-term safety and preliminary efficacy of gene therapy for Leber's congenital amaurosis are described.

Hot spots of retroviral integration in human CD34+ hematopoietic cells.

Genes involved in hematopoietic and immune system development are targeted at high frequency and enriched in hot spots, suggesting that the CD34(+) gene expression program is instrumental in directing RV integration.