Characterization and Delivery of DNA Aptamers Selected for the Prevention of Alpha-Synuclein Aggregation in Parkinson's Disease

Abstract

Aptamers are functional nucleic acids that function in a wide variety of applications, from biosensing to catalysis to therapeutics. Considered functionally analogous to antibodies, aptamers are single-stranded oligonucleotides capable of binding to target molecules with great affinity and specificity. In the field of medicine, the potential biological application of aptamers as a therapeutic or diagnostic is ever growing. Aptamers designed to target α-synuclein, a protein implicated in the pathogenesis of Parkinson's disease due to its propensity to aggregate, were investigated to probe their affinity for the protein as well as their ability to hinder the aggregation of the protein in vitro. Aggregation assays have proven that the presence of the aptamer candidates targeting monomeric α-synuclein stunt the formation of protein fibrils. One promising aptamer from the research, a-syn-1, was successfully packaged into a liposome vesicle modified to cross the blood-brain barrier and used in in vivo applications. The a-syn-1 aptamer has been delivered to the brains of transgenic mice, expressing human α-synuclein, where it has been colocalized with α-synuclein, and ongoing pharmacokinetic studies are being pursued to investigate the lifetime and distribution of the aptamer in a mouse model through extraction and PCR amplification of the aptamer. Analysis of the liposomes used for the packaging and delivery of the aptamer has provided insight into the loading efficiency and production efficiency of liposome batches.