Table 1.
Disease-causing allele-specific silencing by RNAi.
| Disease | Target gene | Target variation | Inducer of RNAi | Competent siRNA(s) carrying mutation site(s) at the central position | Modification | References |
|---|---|---|---|---|---|---|
| Familial Alzheimer's disease | Amyloid precursor protein (APP) | K670N-M671L (Swedish mutant) | synthetic siRNA | yes | no | Miller VM. et al. (2004) [43] Ohnishi Y. et al. (2006) [44] Feng X. et al. (2006) [45] |
| Amyloid precursor protein (APP) | K670N-M671L (Swedish mutant) | synthetic siRNA | no | nucleotide mismatches | Ohnishi Y. et al. (2008) [46] | |
| Amyloid precursor protein (APP) | V717F (London mutant) | synthetic siRNA | yes | no | Ohnishi Y. et al. (2006) [44] | |
| Amyloid precursor protein (APP) | V717I (London mutant) | synthetic shRNA | yes | no | Feng X. et al. (2006) [45] | |
| Preseniline 1 (PSEN1) | L392V | synthetic siRNA | yes | 2-Thiouridine chemical modification | Sierant M. et al. (2011) [47] | |
| Amyotrophic lateral sclerosis (ALS) | Superoxide dismutase (SOD1) | G93A | shRNA expression vector | yes | no | Xia X. et al. (2006) [48] |
| Superoxide dismutase (SOD1) | G85R | synthetic siRNA | yes/no *1 | nucleotide mismatch | Schwarz DS. et al. (2006) [49] | |
| Slow channel congenital myasthenic syndrome (SCCMS) | Acetylcholine receptor (AChR) | aS226F | synthetic siRNA/shRNA | yes | no | Abdelgany A. et al. (2003) [50] |
| Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) | Microtubule-associated protein TAU (MAPT) | V337M | synthetic siRNA | yes | nucleotide mismatch | Miller VM. et al. (2003,2004) [43,51] |
| Ehlers-Danlos syndrome (vEDS) | Procollagen type III (COL3A1) | G252V | synthetic siRNA | yes | no | Muller GA. et al. (2012) [52] |
| Sickle cell anemia | Hemoglobin-beta locus (HBB) | E6V | synthetic siRNA | yes | no | Dykxhoorn DM. et al. (2006) [53] |
| Familial amyloidotic polyneuropathy (FAP) | Transthyretin (TTR) | V30M | synthetic siRNA | yes | no | Kurosawa T. et al. (2005) [54] |
| Fibrodysplasia ossificans progressiva (FOP) | Activin A receptor type I (ACVR1) | R206H, G356D | synthetic siRNA | yes | nucleotide mismatch | Takahashi M. et al. (2012) [55] |
| Activin A receptor type I (ACVR1) | R206H | synthetic siRNA | yes | no | kaplan J. et al. (2012) [56] | |
| Tumors | Phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) | 1633G -> A 3140A -> G | synthetic siRNA | yes | no | Huang H. et al. (2009) [57] |
| Spinocerebellar ataxia type 1 (SCA1) | Ataxin-1 (ATXN1) | flanking region of expanded CAG repeat | shRNA expression vector | N/A *2 | no | Xia H. et al. (2004) [58] |
| Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3) | ATAXIN3/MJD1 | SNPs linked to expanded CAG repeat | synthetic siRNA / shRNA expression vector | yes | no | Miller VM. et al. (2003) [51] Alves S. et al. (2008) [59] Nobrega C. et al. (2013) [60] |
| Spinocerebellar ataxia type 7 (SCA7) | Ataxin-7 (ATXN7) | SNP linked to expanded CAG repeat | shRNA expression vector | no | no | Scholefield J. et al. (2009) [61] |
| Parkinson's disease | Leucine-rich repeat kinase 2 (LRRK2) | R1441G, R1441C | shRNA expression vector | yes | no | de Ynigo-Mojado L. et al. (2011) [62] |
| Leucine-rich repeat kinase 2 (LRRK2) | G20195S | shRNA expression vector | no | no | Sibley CR. et al. (2011) [63] | |
| alpha-synuclein | A30P | shRNA expression vector | no | nucleotide mismatch | Sibley CR. et al. (2011) [63] | |
| Huntington disease | Huntingtin (HTT) | SNPs linked to expanded CAG repeat | synthetic siRNA | yes/no *1 | nucleotide mismatch | Pfister EL. et al. (2009) [64] Takahashi M. et al. (2010) [65] |
*1: Not in some cases. *2: N/A, not applicable.