Related Experiment Video
Updated: May 5, 2026
Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
Published on: September 5, 2016
Therapeutic oligonucleotide ASC1R shows excellent tolerability and remarkable efficacy in reducing SARS-CoV-2 mRNA
Veronika Nemethova1, Petra Babiakova1, Michal Selc2
1Selecta Biotech SE, Bratislava 84107, Slovakia.
Abstract:
The coronavirus pandemic has resulted in over 775 million cases and 7 million deaths worldwide, driving efforts to develop therapeutic strategies to control the viral infection. Therapeutic oligonucleotides have shown promise in treating many pathological conditions, including those of viral origin. The present study assessed the in vivo efficacy and safety of ASC1R, a novel therapeutic oligonucleotide of unconventional design targeting the conserved viral RdRp sequence essential for replication. In functional studies, ASC1R was administered to transfected C57BL/6 mice at doses of 1 and 10 mg/kg. Safety assessments included acute toxicity evaluations at doses ranging from 30 to 100 mg/kg, and subacute toxicity evaluations of repeated doses of 1 and 10 mg/kg. Evaluations included general clinical observations, findings at necropsy, measurements of organ weight, and histopathological examinations of the liver, lungs, spleen, and kidneys. ASC1R effectively reduced RdRp levels >94 % within 24 hours following a single 1 mg/kg dose, with no observed organ toxicity. Acute and subacute toxicity assessments found that mice receiving high (≥30 mg/kg) or repeated (10 mg/kg for 7 days) doses of ASC1R showed an increase in relative spleen weight, without histopathological changes. The marked ability of a single low dose of ASC1R (1 mg/kg) to reduce viral RNA suggests its potential for clinical applications, balancing therapeutic efficacy with minimal side effects. Our findings indicate that ASC1R has promise as a viable treatment option for patients with COVID-19.
Insights
A novel therapeutic oligonucleotide, ASC1R, effectively reduced viral RNA by over 94% at a low dose. This COVID-19 treatment candidate demonstrated efficacy with minimal side effects in preclinical studies.
Area of Science:
- Virology
- Molecular Biology
- Pharmacology
Background:
- The COVID-19 pandemic necessitates novel therapeutic strategies.
- Therapeutic oligonucleotides show potential for treating viral infections.
- ASC1R is a novel oligonucleotide targeting the viral RNA-dependent RNA polymerase (RdRp).
Purpose of the Study:
- To evaluate the in vivo efficacy and safety of ASC1R for potential COVID-19 treatment.
- To assess ASC1R's ability to inhibit viral replication by targeting RdRp.
- To determine the toxicity profile of ASC1R in preclinical models.
Main Methods:
- ASC1R was administered to C57BL/6 mice at doses of 1 and 10 mg/kg.
- Functional efficacy was measured by RdRp level reduction.
- Safety was assessed through acute and subacute toxicity studies, including clinical observations, organ weights, and histopathology.
Main Results:
- A single 1 mg/kg dose of ASC1R reduced RdRp levels by >94% within 24 hours.
- No organ toxicity was observed at effective therapeutic doses.
- High or repeated doses of ASC1R led to increased spleen weight without histopathological changes.
Conclusions:
- ASC1R demonstrates significant potential as a clinical treatment for COVID-19.
- A low single dose of ASC1R effectively reduces viral RNA with a favorable safety profile.
- ASC1R offers a promising therapeutic option balancing efficacy and minimal side effects.
