AntiSense Oligos (ASO): Advanced RNA silencing technology to reduce pathogens and ectoparasites of livestock

Authors: Hunter, Wayne; METZ, JACKIE - Aum Lifetech; Temeyer, Kevin; Perez De Leon, Adalberto - Beto; TOMICH, JOHN - Kansas State University; AISHWARYA, VEENU - Kansas State University

Submitted to: Entomological Society of America Annual Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 7/17/2018
Publication Date: N/A
Citation: N/A

Interpretive Summary: Gene silencing methods using RNA interference (RNAi) are attractive for development of applications for treatment of human and animal disease, however, there are several limitations to effective clinical translation of these technologies, including: (i) inability to target bacterial pathogens, (ii) low stability of RNA molecules, susceptible to nuclease degradation, (III) cytotoxicity when bound to some carriers, like peptides, (iv) difficulty with intracellular delivery of RNAi products. FANA technology utilizes a specific sugar modification on single stranded modified RNAs that can be used for RNA silencing and gene regulation experiments. We report use of FANA-modified antisense oligonucleotides (ASOs) as a potential solution to these problems. In earlier studies, ASOs exhibited suppression of various RNA species activity in a wide spectrum of cellular and animal models. In addition, the FANA-modified ASOS do not require complex formulation or delivery agents, exhibit increased resistance to nuclease degradation, do not exhibit cytotoxicity, and have increased target specificity. In addition, we present evidence that supplementing ASOs with Branched Amphiphilic Peptide Capsules (BAPCs) may increase the persistence of ASOs in whole blood samples. Together, these improved properties demonstrate substantial progress toward development of RNA suppression treatments as animal or human therapeutics.

Technical Abstract: Several challenges have prevented the development and commercialization of biotechnology based on RNA inference (RNAi) which are sequence specific methods for gene silencing making them tremendously attractive applications for human and animal therapeutics. However, there are limitations to effective clinical translation of these technologies. These include: inability to target bacterial pathogens; low stability; susceptible to nuclease degradation; cytotoxicity when bound to some carriers, like peptides; and difficulty with intracellular delivery of RNAi products (siRNA, dsRNA). FANA technology is a 2'-deoxy-2'-fluoro-beta-D-arabinose sugar modification on single stranded antisense oligonucleotides that can be used for RNA silencing and regulation experiments. Reported here are FANA-modified antisense oligonucleotides (ASOs) as a potential solution to the aforementioned limitations. It was shown in earlier studies that ASOs: worked in a wide spectrum of cellular and animal models; suppressed any desired RNA target (siRNA, mRNA, lncRNA, miRNA); FANAASO's were intracellularly delivered without delivery agents (conjugates or formulations); did not cause cytotoxicity, having increased target specificity; and showed increased resistance to nuclease degradation. Through the application of advances in organ and tissue specific delivery, we documented that supplementing ASOs with Branched Amphiphilic Peptide Capsules (BAPCs) may increase the persistence of ASOs in whole blood samples and provide increased efficacy against livestock ectoparasites.