Table 2.
Preclinical CRISPR Therapy in disease models listed in this review.
| Diseases | Target (Gene accession number) | Animal model or substrate | Delivery System | Strategy | Outcome | Author, year, (Refs) |
|---|---|---|---|---|---|---|
| β-thalassemia | HBB (NC_000011.10) | CD34+ HSPCs of β-thalassemia patients | RNP; electroporation | NHEJ-mediated mRNA splicing | 93.0% indel frequency (SpCas9) | Xu et al, 2019 (50) |
| Hemoglobinopathies | BCL11A erythroidenhancer (NC_000002.12) | CD34+ HSPCs from sickle cell disease patient | RNP; electroporation | NHEJ-mediated enhancer disruption | 54.6% reduction of BCL11A expression | Wu et al, 2019, (52) |
| Leber congenital amaurosis type 10 | CEP290 (NC_000012.12 ) | HuCEP290 IVS26 KI mouse eye | AAV; subretinal injection | NHEJ-mediated aberrant splicing | ~ 60% editing rates in mice | Maeder et al, 2019, (53) |
| Duchenne muscular dystrophy (DMD) | Dmd (NC_000086.7) | mdx mice muscle | AAV; intramuscular injection (IM), retro- orbital injection (RO) and intraperitoneal injection (IP) | NHEJ-mediated mutant exon 23 skipping | ~52% of WT (IP) , ~71% of WT (RO), and ~70% of WT (IM) Dystrophin protein levels | Long et al, 2016, (55) |
| Duchenne muscular dystrophy (DMD) | Dmd (NC_000086.7) | mdx mice muscle | AAV; intramuscular injection | NHEJ-mediated mutant exon 23 skipping | ~2% of all alleles from the whole muscle lysate | Nelson et al, 2016, (56) |
| Duchenne muscular dystrophy (DMD) | Dmd (NC_000086.7) | mdx mice muscle | AAV; intraperitoneal injection | NHEJ-mediated mutant exon 23 skipping | 24-47% of total Dmd mRNA in cells including exon23 deletion | Tabebordbar et al, 2016, (57) |
| Congenital muscular dystrophy type 1A (MDC1A) | Lama1 (NC_000083.6 ) | dy2j/dy2j mouse | AAV; intramuscular or tail vein injection | CRISPR activator mediated gene upregulation | 3.6-fold upregulation of Lama1 | Kemaladewi et al, 2019, (60) |
| Hereditary tyrosinemia type I (HTI) |
FAH (NC_000073.6) |
FAHmut/mut mouse liver | AAV combined with lipid nanoparticles; intravenous injection | HDR-mediated point mutation correction | ~0.8% initial correction rate in total liver DNA; more than 6% FAH+ hepatocytes | Yin et al, 2016, (62) |
| Hereditary tyrosinemia type I (HTI) |
FAH (NC_000073.6) |
FAHmut/mut mouse hepatocytes | AAV; transplantation | HDR-mediated point mutation correction | 2.6% alleles were correted | VanLith et al, 2019, (63) |
| Hereditary tyrosinaemiatype I (HTI) |
FAH (NC_000073.6) |
FAHmut/mut mouse liver | plasmids; hydrodynamic tail-vein injection | Adenine base editor mediated point mutation correction | ~0.3% initial correction rate in liver, ~4% FAH+ hepatocytes | Song et al, 2019, (64) |
| α1-antitrypsin deficiency (AATD) | AAT (NC_000078.6 ) |
PiZ mouse liver | AAV; intravenous injection | NHEJ-mediated mutant AAT disruption | ~30% idel frequency | Bjursell et al, 2018, (66) |
| α1-antitrypsin deficiency (AATD) | AAT (NC_000078.6 ) |
PiZ mouse liver | AAV; intravenous injection | HdR-mediated point mutation correction | ~2% correction rate in liver | Song et al, 2018, (67) |
| Perinatal Lethal Respiratory Failure | SFTPC ( NC_000080.6) | SFTPCI73T; R26mTmG/+ mouse fetus lung | adeno virus; intra-amniotic delivery | NHEJ-mediated mutant SFTPC disruption | ~20% editing in the lung epithelium of fetuses | Alapati et al, 2019, (69) |
| Genetic Deafness | Tmc1 (NC_000085.6) | Beethoven (Bth)mouse ear | AAV; Inner-ear injections | NHEJ-mediated mutant Tmc allele disruption | 2.2% indel frequencies at 55 days after injection; 24% decrease in Bth mRNA | György et al, 2019, (75) |