Table 5.

History of viral vector technology for human gene therapy (adapted from [35, 37])

Year	Gene therapy landmark or setback	Year	Gene editing advances
1983	Successful retroviral gene transfer to murine HSCs	1983
1990–1996	First attempted T lymphocyte and HSC gene therapy for ADA-SCID	1996	ZFN architecture described
1997	First attempted HSC gene therapy in CGD	1997
1997–2000	Introduction of conditioning regimens to gene therapy protocols	1997–2000
2000–2002	Successful HSC gene therapy in SCID-X1 and ADA-SCID Mapping of human genome completed	2000–2002
2002–2003	Development of SIN gammaretroviral and lentiviral vector systems for applications to PID	2002–2003
2003	First report of LTR-mediated insertional mutagenesis leading to leukemia	2003
2006	First retroviral vector trial for WAS started	2009	TALEN code described, first ZFN gene edited T cells infused (CCR5/HIV)
2010	Insertional mutagenesis in gammaretroviral trials for WAS and CGD reported	2012	CRISPR/Cas9 system described
2013–2015	Successful SIN gammaretroviral and lentiviral gene therapy in several PIDs	2013	Cas9-gRNA used in mammalian cells
2014	First report of successful ZFNs-mediated editing in HSPCs	2014	ZFN-modified T cell trial reports safety Preclinical HSC gene correction for X-SCID published
2015	Efficacy of lentiviral gene therapy for WAS published	2015	AAV6 identified as a HDR donor delivery platform
2016	First licensed ex vivo gene therapy Strimvelis™ for ADA-SCID	2016	CRISPR/Cas9 efficiency increases using RNP delivery
2017	In vivo retinal gene therapy approved in US (Luxturna-LCA), Kymriah and Yescarta CAR T cell products approved in US	2017	First in vivo ZFN administration (Hunters syndrome)
2019	Zynteglo approved in Europe (LV/beta-thal)	2018	First ex vivo CRISPR gene edited HSC trial initiated (SCD, beta-thal)
2020	Successful LV gene therapy for CGD reported	2019	First in vivo CRISPR/Cas9 administration (LCA10)