TABLE 1.

Developments in retroviral gene therapy vectors.

	Advantages	Disadvantages	Advances	References
Gene therapy	Stable integration and expression of transgene	Oncogenesis	1983 - Creation of retroviral vectors	Perkins et al. (1983),Miller et al. (1983), Joyner and Bernstein, (1983)
	Low immunogenicity	Limited ability to target select genes	1990 - MLV vectors in patients for X-SCID	Blaese et al. (1995),Cavazzana-Calvo et al. (2000)
			2006 - HIV-1 vectors in patients for cancer treatment	Morgan et al. (2006),Bobisse et al. (2009),Johnson et al. (2009)
			2009 - HIV-1 vectors in patients for X-ALD and β-thalassemia	Cartier et al. (2009),Cavazzana-Calvo et al. (2010)
			2018 - CRISPR-CAS9 in patients	Romero et al. (2018)
Fusions of IN	Transduction of primary cells	Potential disruption of intasome multimers	1994 - First chimeric HIV-1 IN fusions	Bushman (1994),Goulaouic and Chow (1996)
	Modification of retroviral protein only	Reduced integration efficiency	1996 - First chimeric ASLV IN fusions	Katz et al. (1996)
			1997 - Zinc finger fusions to HIV-1 IN	Bushman and Miller (1997),Tan et al. (2004)
Fusions of tethering factors	Does not require modification of retroviral proteins	Cannot be performed in primary cells	2003 - Discovery of LEDGF/p75 as HIV-1 IN co-factor	Cherepanov et al. (2003),Turlure et al. (2004)
		Does not redirect all integration events	2009 - First LEDGF/p75 fusions	Meehan et al. (2009),Ferris et al. (2010),Silvers et al. (2010)
		Requires manipulation of cellular factors	2013 - Discovery of BET proteins as MLV IN co-factors	De Rijck et al. (2013),Gupta et al. (2013),Sharma et al. (2013)
			2013 - LEDGF/p75 fusion employed in WT cells	Vets et al. (2013)
Tether independent targeting	Transduction of primary cells	Limited efficacy	2016 - Alterations to PFV GAG	Hocum et al. (2016)
	No cellular modifications required		2014 - Alterations to MLV IN	Aiyer et al. (2014),Larue et al. (2014),El Ashkar et al. (2014)