mRNA Cell Engineering Enables Rapid Prototyping of Macrophage Gene-Editing Strategies for Cancer Immunotherapy Applications
Macrophages’ ability to infiltrate solid tumors and engage in both direct killing of cancer cells and recruitment of other immune cells has made them a promising target for development of next-generation cancer immunotherapies. The innate ability of macrophages to ingest foreign genetic material also facilitates their engineering with formulated nucleic acids, including mRNA. The oncoantigen […]
Novel Ionizable Lipids Derived from 2-Hydroxypropylamine and Spermine for mRNA-LNP Delivery
Lipid nanoparticles (LNPs) containing cationic or ionizable lipids offer several advantages compared to other vehicles for nucleic acid delivery and have seen expanded clinical use with the introduction the COVID-19 mRNA vaccines and in treatments for genetic diseases. However, poor targeting, insufficient cellular uptake, and low endosomal release currently limit the use of lipid nanoparticles […]
Directed Differentiation of Gene Edited iPSCs by Small-Molecule Inhibition of a Transgene-Encoded Protein
Indoleamine 2,3-dioxygenase 1 (IDO1) is an inducible, heme-containing enzyme that is critically involved in tryptophan catabolism and known to be a prominent immune regulator. Cell therapies with increased IDO1 expression are of high interest for a variety of indications, including autoimmune disorders, inflammatory diseases, transplant recovery, and wound healing. In particular, iPSC-derived mesenchymal stem cells […]
A Scalable, iPS Cell Derived Lymphocyte and Myeloid Multi-Cell-Type Therapeutic Platform for Enhanced Tumor Cell Killing
Induced pluripotent stem (iPS) cell therapies have the potential to treat a wide variety of devastating diseases. iPS$ cell-derived lymphocytes (e.g., T cells and NK cells) engineered to express targeting molecules such as chimeric antigen receptors (CARs) have shown clinical promise to treat hematological malignancies. More recently, iPS cell-derived myeloid cells are being developed to […]
Chemically Modified Single-Stranded DNA Donors Enable Efficient mRNA Gene Editing-Mediated Knock-In in Human iPS Cells
Genome-editing technology provides a means of modifying genes in living cells, and is being explored for the development of therapies to treat cancer and a variety of genetic disorders. Gene-editing proteins can be used to create single- and double-strand breaks at specific genomic sites for knocking out a gene or, when combined with an exogenous […]
Efficient Transgene Knock-In in Human iPS Cells Combined With Small Molecule-Mediated “On-Switch” Yields Clonal Populations of Engineered Tissue-Specific Cells
Mesenchymal stem cells (MSCs) are a promising cell-therapy platform with the potential to treat a diverse array of diseases due to their immunomodulator properties – properties which can be enhanced through gene editing. Gene editing autologous or donor- derived MSCs is challenging due to the non-clonal nature of these cell sources, and associated risks of […]