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Gene therapy has come a long way since its first proof-of-concept experiments in the 1990s. In the past decade the approach — which involves fixing or replacing a disease-causing gene or changing its activity — has evolved, matured and advanced at a rapid pace.
Non-viral vehicles for the delivery of nucleic acids have potential applications for the treatment of diseases by, for example, restoring, correcting or silencing the expression of genes. In this Review, the authors discuss the latest developments in synthetic materials used for gene delivery and the challenges that must be overcome to transfer these innovations into the clinic.
Adeno-associated virus (AAV) vector-mediated gene delivery has had long-term therapeutic effects for several diseases, including haemophilia and Duchenne muscular dystrophy. Genetically modifying AAV vectors to increase their transduction efficiency, vector tropism and ability to avoid the host immune response may further increase the success of AAV gene therapy.
This Review discusses strategies for the genetic engineering of adoptive T cell immunotherapies with a focus on approaches harnessing transgenic T cell receptors or chimeric antigen receptors to treat cancer. The authors also discuss the more complex levels of genetic regulation that will be needed to ensure both safety and efficacy.
Haematopoietic stem and progenitor cell (HSPC) gene therapy using lentiviral or gammaretroviral vectors has now been approved for clinical use. In this Review, Ferrari, Thrasher and Aiuti discuss the history of HSPC gene therapy, the clinical promise of gene-editing HPSCs and the use of HSPC gene therapy to treat specific diseases.
Wilkinson and colleagues discuss haematopoietic stem cell (HSC) self-renewal in mice and humans. Experimental techniques for assaying HSC self-renewal are addressed, along with biological mechanisms regulating HSC self-renewal in vivo and ex vivo, and the therapeutic implications of this understanding.