SNCA and neurodegenerative disease: Binding affinity between different sgRNAs and relative position to the TSS are critical for CRISPRi. dCas9 can be used for gene expression manipulations and gene contributions of neurodegenerative disease.CRISPR/dCas9-KRAB and TSS2-1 sgRNA expression reduced endogenous alpha-synuclein mRNA levels in SNCA-tri iPSC-derived neurons by 40%.