Lentiviral vectors as the delivery vehicles for transduction into iPSCs

Over the last decade, the generation and differentiation of induced pluripotent stem cells (iPSCs) from somatic cells highlights one of the most groundbreaking discoveries in science and medicine. iPSCs has become an indispensable tool for elucidating a pathology of different diseases, drug screening, and development. A critical step for advancing iPSC technology is the establishment of delivery systems for introducing reprogramming factors into embryonic and somatic cells. Retroviral and lentiviral vectors are among the most common delivery vehicles used to induce iPSCs generation and differentiation, due to their ability to stably transduce a broad range of postmitotic cells and mediate high levels of gene expression. Nevertheless, integration capacity of the vectors increases a risk of insertional mutagenicity and oncogenicity and thus raises serious safety concerns regarding their use in clinical studies. Furthermore, residual transgene expression in virus‐carrying human iPSCs can alter the differentiation potential of the cells and profoundly affect their molecular characteristics. Integrase-deficient viruses including adenoviruses (Ad), Sendai virus–based vectors (SeVs), and integrase-deficient lentiviral vectors (IDLVs) provide valuable alternative to the integrase-competent counterparts, and as such are under intensive development and exploration. In this chapter (i) we provide a systemic overview of retroviral and lentiviral vectors employed for the generation and differentiation of iPSCs; (ii) we discuss construction of the vectors harboring reprogramming factor combinations; (iii) we outline in detail pros and cons of integrating viruses for iPSC generation; (iv) we will highlight the progress made in the field of nonintegrating vectors developed for the iPSCs production and differentiation.