ASGT Press Release

This is the press release for the February 1, 2002, issue of Molecular Therapy (Volume 5, Number 2), the journal of the American Society of Gene Therapy (ASGT). Molecular Therapy is owned and copyrighted by the ASGT, and published monthly by Academic Press/Elsevier Science.

This information is not embargoed (see embargo policy below). Please cite Molecular Therapy as the source of this information.

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On the cover: Proteins out the nose
One fundamental application of gene therapy is to provide a constant and efficacious source of protein replacement in inherited and acquired diseases. This has proved more difficult than initially thought, although recent reports of positive results in ongoing clinical trials for hemophilia are promising.

In this issue of Molecular Therapy, Eric Alton of the Imperial College School of Medicine in London and his collaborators describe a gene delivery system that has clinical promise for many diseases. By infecting mouse nasal epithelial cells with a recombinant Sendai virus vector encoding the anti-inflammatory cytokine protein interleukin-10, they were able to obtain clinically relevant systemic levels of IL-10. This relatively noninvasive site of infection, combined with the efficiency of Sendai virus vectors, could potentially be applied to deliver genes encoding blood-clotting factors, immune stimulators or modulators, or even insulin.

Griesenbach, et al. (2002). The nasal epithelium as a factor for systemic protein delivery. Mol. Ther. 5: 98-103.

Getting in the door
Although synthetic (i.e., nonviral) vectors are an attractive option to viral vectors for several reasons, current formulations just cannot match the ability of viruses to traverse the cell membranes, limiting the effectiveness of nonviral approaches to date. Karola Rittner of Transgene, S.A., in Strasbourg, France and his collaborators announce a "break through" the membrane gate. They have developed a series of short peptides (of 20 amino acids) that both bind to DNA and destabilize membranes to allow passage. Although similar molecules have been described to work in vitro, Rittner et al. show that their peptides are superior to previous versions AND are highly efficient in transferring genes in vivo in mice.

The further refinement and characterization of such vectors remain to be done, but these results are a boost to all nonviral gene therapy research. Rittner, et al. (2002). 

New basic, membrane-destabilizing peptides for plasmid-based gene delivery in vitro and in vivo. Mol. Ther. 5: 104-114.

Adenovirus and immunity
Despite much negative press, the use of recombinant adenovirus as a vector for delivering genes remains the subject of a great deal of active research, particularly in anti-cancer applications. Many of these studies use adenovirus to deliver genes to tumors to enhance the patient's immune response against the tumor itself. However, it appears that adenovirus can perform some of this function without carrying along any therapeutic genes.

Melanie Ruzek and her collaborators at Genzyme Corporation in Framingham, MA, describe a series of studies that demonstrate that adenoviral vectors in their own right can stimulate significant innate immune responses against tumors. These responses, provoked by intact but "empty" (i.e., non-transgene-bearing) adenovirus particles, delay tumor growth in mouse models of melanoma. Thus, at least part of the immune response seen in adenoviral anti-cancer trials and research is due to the vector delivery system itself, apart from any transgene also delivered. Far from being a liability of the system, this property can probably be exploited to further enhance the anti-tumor capabilities of the patient's own immune system. It also underlines the important clinical role adenovirus can still play in the gene therapy of specific diseases.

Ruzek, et al. (2002). Adenoviral vectors stimulate murine natural killer cell responses and demonstrate antitumor activities in the absence of transgene infection. Mol. Ther. 5: 115-124.

Other items of interest:

Editorial: Biopiracy: Distrust widens the rich-poor divide
Editor-in-Chief Inder Verma considers the current problems facing "bioprospecting."

Commentary: Adenosine deaminase gene therapy protocol revisited 
Donald Kohn of Children's Hospital, Los Angeles, relates the results from a current ADA trial and suggests that, perhaps, the design of the first official human gene therapy trial for this disease may have inadvertently covered up its success..

EMBARGO POLICY:
Molecular Therapy considers the embargo lifted upon editorial acceptance of a manuscript (i.e., the decision of the editor to accept a manuscript following successful peer review and revision). We make every effort to have manuscripts published electronically before print. Manuscripts still under review should not be reported as being published in Molecular Therapy.

Fintan R. Steele, Ph.D.
Editor, Molecular Therapy
Executive Editor, Genomics
Academic Press
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fsteele@acad.com
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