Native and engineered tropism of vectors derived from a rare species D adenovirus serotype 43

Unique molecular properties of species D adenoviruses (Ads)-the most diverse yet underexplored group of Ads-have been used to develop improved gene vectors. The low seroprevalence in humans of adenovirus serotype 43 (Ad43), an otherwise unstudied species D Ad, identified this rare serotype as an attractive new human gene therapy vector platform. Thus, in this study we wished to assess biological properties of Ad43 essential to its vectorization. We found that (1) Ad43 virions do not bind blood coagulation factor X and cause low random transduction upon vascular delivery; (2) they clear host tissues more quickly than do traditionally used Ad5 vectors; (3) Ad43 uses CD46 as primary receptor; (4) Ad43 can use integrins as alternative primary receptors. As the first step toward vectorization of Ad43, we demonstrated that the primary receptor specificity of the Ad43 fiber can be altered to achieve infection via Her2, an established oncotarget. Whereas this modification required use of the Ad5 fiber shaft, the presence of this domain in chimeric virions did not make them susceptible for neutralization by anti-Ad5 antibodies

How does serif vs sans serif typeface impact the usability of e-commerce websites?

This work was funded by the Department of Science, Innovation, and Universities (Spain) under the National Program for Research, Development, and Innovation (project RTI2018-099235-B-I00). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings

Various studies have emphasized an immunodepression state observed at the tumour site. To reverse this defect and based upon animal studies, we initiated a phase I clinical trial of gene therapy in which various doses of xenogeneic monkey fibroblasts (Vero cells) genetically engineered to produce human IL-2 were administered intratumorally in 8 patients with metastatic solid tumours. No severe adverse effect was observed in the 8 patients analysed during this clinical trial even in the highest dose (5 ¥ 107 cells) group. This absence of toxicity seems to be associated with rapid elimination of Vero-IL-2 cells from the organism. Indeed, exogenous IL-2 mRNA could no longer be detected in the peripheral whole blood 48 hours after Vero-IL-2 cell administration. In addition, we did not find any expression of exogenous IL-2 mRNA in post-therapeutic lesions removed 29 days after the start of therapy. A major finding of this trial concerns the two histological responses of two treated subcutaneous nodules not associated with an apparent clinical response. The relationship between local treatment and tumour regression was supported by replacement of tumour cells by inflammatory cells in regressing lesions and marked induction of T and natural killer cell derived cytokines (IL-2, IL-4, IFNg …) in post-therapeutic lesions analysed 28 days after the start of Vero-IL-2 administration. Gene therapy using xenogeneic cells as vehicle may therefore present certain advantages over other vectors, such as its complete absence of toxicity. Furthermore, the in vivo biological effect of immunostimulatory genes, i.e IL-2-, may be potentiated by the xenogeneic rejection reaction. © 2000 Cancer Research Campaign http://www.bjcancer.co

Les systèmes alternatifs de production d’anticorps monoclonaux thérapeutiques

Les anticorps monoclonaux thérapeutiques commercialisés ou en développement sont produits à partir de cellules de mammifères en culture, dont notamment la cellule de hamster CHO. Ces systèmes cellulaires permettent la production industrielle de protéines complexes possédant des structures, activités biologiques et propriétés pharmacodynamiques proches des protéines naturelles. Mais des coûts de production élevés et un prix du traitement prohibitif pourraient dans l’avenir limiter l’accessibilité de ces thérapies innovantes au plus grand nombre et freiner ce marché pourtant en très fort développement. Parallèlement à l’optimisation de la productivité des systèmes mammaliens, l’industrie pharmaceutique et biotechnologique développe activement des systèmes de production alternatifs espérés moins coûteux, plus efficaces et permettant une amélioration de l’efficacité thérapeutique des anticorps thérapeutiques

Contester la métropolisation dans les urnes : retour sur la campagne de la liste « Nantes en Commun·e·s » au scrutin municipal de 2020

International audienc

Les genes de maintenance : etude du gene HMGCoA reductase in vitro et dans les souris transgeniques

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc