May 2021 | Lentivirus Research Production

The stem cell toolkit and its application in developing next-generation stem cells.
 Virus-mediated transduction of stem cells (target cell), particularly with self-inactivating lentiviruses, is a useful tool for the creation/development of next-generation stem cells. Viruses can be used to engineer: prodrug-converting enzymes, oncolytic viruses and other anticancer drugs into neural stem cells (NSCs) and mesenchymal stem cells (MSCs) (part a); optogenetically enhanced stem cell derivatives to provide light-inducible control over the activity of trans-planted stem cells/progenitors (part b); chimeric antigen receptor (CAR)-expressing haematopoietic stem cells (HSCs) and pluripotent stem cell (PSC)-derived natural killer (NK) cells for immune-oncology applications (part c); gene therapy in HSC, skin and muscle progenitors to treat inherited diseases (part d); and cytokine/growth factor delivery in MSCs/neural progenitors to stimulate endogenous tissue repair (part e). Click chemistry is another engineering tool that can be used to tether anticancer agents to stem cells for improved delivery to hard-to-reach cancers, such as leukaemia cells residing deep in the bone marrow (part f). Advances in gene editing technology have made this a versatile tool to precisely edit specific loci within the genome, and gene editing technology has become the tool of choice for the creation/development of universally immunocompatible PSC lines and derivatives (part g). Several of these next-generation stem cell-based therapies have already reached clinical testing, whereas others in preclinical development are not far behind. AAV, adeno-associated virus; DBCO, dibenzocyclooctyne; HLA, human leukocyte antigen; PD-L1, programmed cell death protein 1 ligand. (Figure 1, Nature Reviews Drug Discovery 19, 463–479 (2020))


Figure reprinted with permission from Springer Nature

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