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Capsid modification strategies for detargeting adenoviral vectors.
Parker, Alan L; Bradshaw, Angela C; Alba, Raul; Nicklin, Stuart A; Baker, Andrew H.
Afiliação
  • Parker AL; Institute of Cancer and Genetics, Cardiff University, Cardiff, UK.
Methods Mol Biol ; 1089: 45-59, 2014.
Article em En | MEDLINE | ID: mdl-24132476
Adenoviral vectors hold immense potential for a wide variety of gene therapy based applications; however, their efficacy and toxicity is dictated by "off target" interactions that preclude cell specific targeting to sites of disease. A number of "off target" interactions have been described in the literature that occur between the three major capsid proteins (hexon, penton, and fiber) and components of the circulatory system, including cells such as erythrocytes, white blood cells, and platelets, as well as circulatory proteins including complement proteins, coagulation factors, von Willebrand Factor, p-selectin as well as neutralizing antibodies. Thus, to improve efficacious targeting to sites of disease and limit nonspecific uptake of virus to non-target tissues, specifically the liver and the spleen, it is necessary to develop suitable strategies for genetically modifying the capsid proteins to preclude these interactions. To this end we have developed versatile systems based on homologous recombination for modification of each of the major capsid proteins, which are described herein.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenovírus Humanos / Proteínas do Capsídeo / Vetores Genéticos Limite: Humans Idioma: En Revista: Methods Mol Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2014 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenovírus Humanos / Proteínas do Capsídeo / Vetores Genéticos Limite: Humans Idioma: En Revista: Methods Mol Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2014 Tipo de documento: Article País de publicação: Estados Unidos