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Molecular design for recombinant adeno-associated virus (rAAV) vector production.
Aponte-Ubillus, Juan Jose; Barajas, Daniel; Peltier, Joseph; Bardliving, Cameron; Shamlou, Parviz; Gold, Daniel.
Afiliação
  • Aponte-Ubillus JJ; Biomarin Pharmaceutical Inc., 105 Digital drive, Novato, CA, 94949, USA. Juan.aponte@bmrn.com.
  • Barajas D; Keck Graduate Institute of Applied Life Sciences, 535 Watson drive, Claremont, CA, 91711, USA. Juan.aponte@bmrn.com.
  • Peltier J; Biomarin Pharmaceutical Inc., 105 Digital drive, Novato, CA, 94949, USA.
  • Bardliving C; Biomarin Pharmaceutical Inc., 105 Digital drive, Novato, CA, 94949, USA.
  • Shamlou P; Keck Graduate Institute of Applied Life Sciences, 535 Watson drive, Claremont, CA, 91711, USA.
  • Gold D; Keck Graduate Institute of Applied Life Sciences, 535 Watson drive, Claremont, CA, 91711, USA.
Appl Microbiol Biotechnol ; 102(3): 1045-1054, 2018 Feb.
Article em En | MEDLINE | ID: mdl-29204900
ABSTRACT
Recombinant adeno-associated virus (rAAV) vectors are increasingly popular tools for gene therapy applications. Their non-pathogenic status, low inflammatory potential, availability of viral serotypes with different tissue tropisms, and prospective long-lasting gene expression are important attributes that make rAAVs safe and efficient therapeutic options. Over the last three decades, several groups have engineered recombinant AAV-producing platforms, yielding high titers of transducing vector particles. Current specific productivity yields from different platforms range from 103 to 105 vector genomes (vg) per cell, and there is an ongoing effort to improve vector yields in order to satisfy high product demands required for clinical trials and future commercialization.Crucial aspects of vector production include the molecular design of the rAAV-producing host cell line along with the design of AAV genes, promoters, and regulatory elements. Appropriately, configuring and balancing the expression of these elements not only contributes toward high productivity, it also improves process robustness and product quality. In this mini-review, the rational design of rAAV-producing expression systems is discussed, with special attention to molecular strategies that contribute to high-yielding, biomanufacturing-amenable rAAV production processes. Details on molecular optimization from four rAAV expression systems are covered adenovirus, herpesvirus, and baculovirus complementation systems, as well as a recently explored yeast expression system.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cultura de Vírus / Dependovirus / Vetores Genéticos Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cultura de Vírus / Dependovirus / Vetores Genéticos Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article