Gene therapy for primary immune deficiencies: a Canadian perspective

Table 1 Preclinical studies of GT for other PID

Condition	Gene defect	Delivery	Achievements and challenges	References
Recombination activating gene 1 and 2 deficiency	RAG-1 and RAG-2	SIN LV	Insufficient expression in vivo causing Omenn’s syndrome	[48, 49]
Artemis deficiency	DCLRE1C	SIN LV	Artemis deficient- mice and human stem cells differentiated in vivo into functional T and B cells	[50]
CD3gamma deficiency	CD3γ	Retro	Constitutive IL-2 synthesis	[51]
Reticular dysgenesis	AJ2	SIN LV	Limited in vitro data	[52]
Purine nucleoside phosphorylase deficiency	PNP	SIN LV	Transient effect in vivo	[53]
ZAP70 deficiency	ZAP70	LV, electroporation	Direct delivery into the thymus	[54, 55]
MHC class II deficiency	CIITA	RV	No recent studies. Concerns about autoimmunity	[56]
HyperIgM syndrome	CD40 ligand	SIN LV TALEN	Targeted CD40 ligand insertion to prevent uncontrolled activation	[57, 58]
IPEX syndrome	FOXP3	LV	Delivery into peripheral T cells	[59]
HLH	PRF	SIN LV	High % of gene corrected cells or high level of perforin expression required in vivo	[60, 61]
XLP	SH2D1A	LV	Incomplete immune reconstitution in vivo, non-physiological expression	[62]
XLA	BTK	TALEN	Corrected mutation and phenotype in vivo	[63]

SIN self inactivating, LV lentivirus, RV retrovirus, IPEX immune dysregulation, polyendocrinopathy, enteropathy X Linked, XLP X linked lymphoproliferative disease, XLA X linked agammaglobulinemia

ISSN: 1710-1492