RNA aptamers for capturing early species of aberrant protein aggr | 60007
Journal of Infectious Diseases & Preventive Medicine

Journal of Infectious Diseases & Preventive Medicine
Open Access

ISSN: 2329-8731

RNA aptamers for capturing early species of aberrant protein aggregates in neurodegenerative diseases

Virtual Meet on Emerging Diseases 2021 & Structural Biology 2021

October 22, 2021 WEBINAR

Elsa Zacco

Istituto Italiano di Tecnologia, Italy

Scientific Tracks Abstracts: J Infect Dis Preve Med

Abstract :

Aptamers are short, single-stranded oligonucleotide sequences capable of binding specific protein targets with high affinity and selectivity, representing a promising tool for both diagnostics and therapeutics. This work illustrates the rational design of de-novo RNA aptamers able to recognize efficiently their protein target at all stages of its maturation to full aggregate species. TDP-43, an essential RNA-binding protein whose aberrant aggregation are associated with up to 97% of sporadic cases of amyotrophic lateral sclerosis (ALS), was selected as target. In vitro validation of the binding strength of the RNA aptamers towards TDP-43 identified binding constants in the nM scale. In association with super-resolution microscopy, the RNA aptamers were employed to successfully visualize all oligomeric state of TDP-43 in vitro, from the smallest oligomeric species to largest aggregates. Transfection of the aptamers in mammalian cellular models recapitulating ALS phenotype demonstrated that they co-localize with both soluble and aggregated TDP-43 in a precise and selective manner. The employment of the RNA aptamers to stain TDP-43 inclusions in ALS patients’ cortical sections allowed for the identification of aggregates as small as 10 nm and for the definition their size and shape. The high specificity of targeting renders the RNA aptamers designed in such fashion a tool with extremely high potential in the diagnostic of proteinopatic diseases at the earliest stages of the development.

Biography :

Elsa Zacco research focus is the investigation of the effect of RNA in protein phase separation. My interest sparkled during my post-doc at King’s College London, when I specialized in the investigation of protein aggregation and the role that RNA may play in it. My research supports the thesis that RNA plays a central role at post-transcriptional regulation and often determines the fate of ribonucleoprotein complexes. My expertise is to investigate the structural-functional interplay between proteins and RNA and unveiling the molecular mechanisms of their interactions. I am currently a senior Marie Curie research fellow at the Italian Institute of Technology, where I am addressing my expertise towards dysfunction of protein-RNA interactions in neurological disorders.