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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1047-x) contains supplementary material, which is available to authorized users.
Highlights
Genetic modification has played a major role in cell biology studies aiming to describe cellular mechanisms and pathophysiological processes
*Correspondence: mbonamino@inca.gov.br †José Eduardo Vargas and Leonardo Chicaybam contributed to the work 2 Programa de Carcinogênese Molecular, Instituto Nacional de Câncer (INCA), Rua Andre Cavalcanti 37/6o andar, Centro, Rio de Janeiro 20231‐050, Brazil Full list of author information is available at the end of the article shRNA and genetic edition of DNA usually require transient or permanent expression for their effects to take place, the permanent expression from a transgenic unit usually requires it to be integrated in the genetic material of the organism so it can be passed from the originally modified cells to the daughter cells
Retroviral integration pattern, a potential problem for gene therapy Provirus integration for Moloney leukemia virus (MLV) is mainly described in promoter and enhancer sequences of the target cell genome, while lentiviral vectors preferentially integrate throughout gene sequences [75,76,77]
Summary
Genetic modification has played a major role in cell biology studies aiming to describe cellular mechanisms and pathophysiological processes. We focus mainly in the available systems and efforts to genetically modify cells through the use of tools such as gammaretro and lentiviral vectors and transposons that currently or potentially accomplish safety and efficiency requirements for clinical applications in gene therapy protocols.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
