title: Retroviral vectors and transposons for stable gene therapy: advances, current challenges and perspectives.
abstract: Gene therapy protocols require robust and long-term gene expression. For two decades, retrovirus family vectors have offered several attractive properties as stable gene-delivery vehicles. These vectors represent a technology with widespread use in basic biology and translational studies that require persistent gene expression for treatment of several monogenic diseases. Immunogenicity and insertional mutagenesis represent the main obstacles to a wider clinical use of these vectors. Efficient and safe non-viral vectors are emerging as a promising alternative and facilitate clinical gene therapy studies. Here, we present an updated review for beginners and expert readers on retro and lentiviruses and the latest generation of transposon vectors (sleeping beauty and piggyBac) used in stable gene transfer and gene therapy clinical trials. We discuss the potential advantages and disadvantages of these systems such as cellular responses (immunogenicity or genome modification of the target cell) following exogenous DNA integration. Additionally, we discuss potential implications of these genome modification tools in gene therapy and other basic and applied science contexts.
authors.affiliation: Centro Infantil-Pontifícia Universidade Católica do Rio Grande do Sul-PUCRS, Porto Alegre, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Vargas
authors.affiliation: Programa de Carcinogênese Molecular, Instituto Nacional de Câncer (INCA), Rua Andre Cavalcanti 37/6º andar, Centro, Rio de Janeiro, 20231-050, Brazil.|Vice-presidência de Pesquisa e Laboratórios de Referência, Fundação Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Chicaybam
authors.affiliation: Centro Infantil-Pontifícia Universidade Católica do Rio Grande do Sul-PUCRS, Porto Alegre, Brazil.
authors.forename: Renato Tetelbom
authors.initials: RT
authors.lastname: Stein
authors.affiliation: Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
authors.affiliation: Grupo de estudo de Expressão Gênica de Eucariotas, Unipampa, Sao Gabriel, Brazil.
authors.forename: Andrés
authors.initials: A
authors.lastname: Delgado-Cañedo
authors.affiliation: Programa de Carcinogênese Molecular, Instituto Nacional de Câncer (INCA), Rua Andre Cavalcanti 37/6º andar, Centro, Rio de Janeiro, 20231-050, Brazil. mbonamino@inca.gov.br.|Vice-presidência de Pesquisa e Laboratórios de Referência, Fundação Instituto Oswaldo Cruz, Rio de Janeiro, Brazil. mbonamino@inca.gov.br.
authors.forename: Martin H
authors.identifier: 0000-0002-4416-5822
authors.initials: MH
authors.lastname: Bonamino
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004251:DNA Transposable Elements / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000378:metabolism*; D006801:Humans; D012190:Retroviridae / Q000235:genetics*; D019895:Transposases / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D019895:Transposases
keywords: Clinical trials; Gene therapy; Lentivectors; Transposons