Antiviral immunity and nucleic acid sensing in haematopoietic stem cell gene engineering

• Published in: Gene therapy Vol. 28; no. 1-2; pp. 16 - 28
• Main Authors: Piras, Francesco, Kajaste-Rudnitski, Anna
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2021; Nature Publishing Group
• Subjects: 631/250/262; 631/532/1542; Antiviral drugs; Biomedical and Life Sciences; Biomedicine; Cell Biology; Gene Expression; Gene manipulation; Gene Therapy; Genetic aspects; Genetic engineering; Genetic Therapy; Genetic Vectors; Health aspects; Hematopoietic Stem Cells; Host-virus relationships; Human Genetics; Humans; Immunity; Innate immunity; Methods; Nanotechnology; Nucleic acids; Nucleic Acids - genetics; Progenitor cells; Review; Review Article; Stem cell research; Vectors; Italy
• ISSN: 0969-7128; 1476-5462; 1476-5462
• DOI: 10.1038/s41434-020-0175-3

The low gene manipulation efficiency of human hematopoietic stem and progenitor cells (HSPC) remains a major hurdle for sustainable and broad clinical application of innovative therapies for a wide range of disorders. Given that all current and emerging gene transfer and editing technologies are bound to expose HSPC to exogenous nucleic acids and most often also to viral vectors, we reason that host antiviral factors and nucleic acid sensors play a pivotal role in the efficacy of HSPC genetic manipulation. Here, we review recent progress in our understanding of vector–host interactions and innate immunity in HSPC upon gene engineering and discuss how dissecting this crosstalk can guide the development of more stealth and efficient gene therapy approaches in the future.