Examples of Stem Cell-Based Therapy in Development Genetically Edited Stem Cells in Clinical Trials And in Preclinical Development Stem cells
Locus/loci edited
In preclinical development β2-Microglobulin hESCs (B2M)
Editing method
AAV
Human iPSCs
B2M, CIITA
CRISPR–Cas9
Human iPSCs
HLAA, HLAB, HLAC
CRISPR–Cas9
Human iPSCs
Various
AAV, ZFN, TALENs, CRISPR
Purpose or indication
Study details
Generation of HLA- A , HLA- B and HLA- C null PSCs with overexpressed HLA- E to escape allogeneic immunogenicity Generation of HLA class I and II null PSCs with overexpressed CD47 to escape allogeneic immunogenicity Allele- specific HLA- A , HLA- B and HLA- C disruption to make HLA class I pseudo- homozygous PSCs or disruption of HLA- A and HLA- B with preservation of HLA- C to avoid allogeneic immunogenicity Correction of genetic mutations in patient- specific iPSCs to potentially treat monogenic diseases
Preclinical studies in humanized mice Preclinical studies in humanized mice
Preclinical studies in immunodeficient mice with human CD8+ T cell challenge In vitro proof of concept and Reviewed early preclinical development
In clinical development
ZFN Autologous HSCs
BCL11A enhancer region
CRISPR–Cas9 CRISPR–Cas9
Autologous HSCs
CCR5
ZFN
Re- expression of fetal haemoglobin to treat β- thalassaemia Re- expression of fetal haemoglobin to treat β- thalassaemia Re- expression of fetal haemoglobin to treat sickle cell anaemia Knockout CCR5 to block HIV entry into T cells derived from edited HSCs
Phase I/II clinical trial (NCT03432364) Phase I/II clinical trial (NCT03655678) Phase I/II clinical trial (NCT03745287) Phase I/II clinical trial (NCT02500849)
Reference: Erin A. Kimbrel and Robert Lanza, Nature reviews, 2020
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