Table 1.

Preclinical experimental studies to knock down SNCA expression using nucleic acid medicine

Reference	Oligonucleotides	Model	Outcome
Hayashita-Kinoh et al. (2006) [4]	AAV-ribozyme	MPP+-treated PD model rat	Survival of TH-positive neurons in the SN
Sapru et al. (2006) [5]	Lenti-shRNA	Rat overexpressing hSNCA in the striatum by lentivirus vector	Silencing SNCA protein in striatal neurons
Gorbatyuk et al. (2010) [6]	AAV-shRNA	WT rat	Neurodegeneration in the SN
Khodr et al. (2011) [7]	AAV-shRNA	Rat overexpressing hSNCA in the SN by AAV	Amelioration of behavioral deficit and DA neuron loss
Kohdr et al. (2014) [8]	miRNA	Rat overexpressing hSNCA in the SN by AAV	Amelioration of behavioral deficit and inflammation
Zharikov et al. (2015) [9]	AAV-shRNA	WT rat/rotenone-exposed rat	35% SNCA knockdown in the SN, improvement of motor function, and protection of DA neurons
Lewis et al. (2008) [10]	siRNA	WT mouse	Moderate reduction of SNCA in the hippocampus
Cooper et al. (2014) [11]	Exosomal siRNA	WT mouse/hSNCA transgenic mouse	50% reduction of SNCA in the midbrain and striatum
Helmschrodt et al. (2017) [12]	PEI/siRNA complex	hSNCA transgenic mouse	65% SNCA knockdown in the striatum
McCormack et al. (2010) [13]	siRNA	WT monkey	40 to 50% SNCA knockdown in SN

AAV = adeno-associated virus; DA = dopaminergic; MPP⁺ = 1-methyl-4-phenylpyridinium; PEI = polyethylenimine; SN = substantia nigra; TH = tyrosine hydroxylase; WT = wild-type