A big opportunity with small RNA

Precision Therapies

give the best patient outcomes

Uncovering Molecular Pathology

unlocks therapeutic opportunities

Deciphering the Heterogeneity of Disease

is the key to success

Small RNAs

are the answer

Small RNAs in drug development

Fastest growing area of research

4x

growth in sRNA focused biomaker publications over the last decade1

3%

of clinical trials in 2020 used sRNA biomarkers2

34
ODN drugs in active clinical trials3
9
FDA Approved ODN therapeutics4

Successful drug development requires a comprehensive view of sRNA biology

Powerful...

sRNA regulates all gene expression, driving disease and maintaining health

…but Complex

functionality is contextual, requiring a full picture of sRNA biology

Current approaches miss important aspects of sRNA biology

  • Annotation of transcript variants and non-templated nucleotides
  • Predicting regulatory targets and mechanism of action
  • Differential regulatory targets based on sRNA variants
  • Extracellular and cellular sRNA localization signals

Starting at the source: how sRNA variants drive disease3

GUIDED BY THE RISC COMPLEX, NON-CODING sRNAs IN THE GENOME MODIFY PROTEIN EXPRESSION

These sRNAs make up 80% of the genome and are crucial in human health and disease3,4

ANALYSIS OF RISC SHOWS THERE ARE MANY CLASSES OF FUNCTIONAL SMALL RNAS

All other sRNA 94%

Only 6% of non-coding sRNAs contained in the RISC complex are miRNA

SINGLE NUCLEOTIDE VARIANTS IN THESE SMALL RNAs DRIVE DISEASE BY DISRUPTING PROTEIN EXPRESSION

sRNA_isoform_variability

sRNA processing errors

Non-templated nucleotide additions

Polymorphic variants or RNA editing

'Seed' sequence – directs RISC to target site RNA

Current data processing and annotation methods condense and obscure the sRNA that inform disease heterogeneity

Next: Applying the approach to accelerate R&D

REFERENCES:
1. National Center for Biotechnology Information. Accessed June 16, 2021. https://pubmed.ncbi.nlm.nih.gov/
2. National Library of Medicine. Accessed June 16, 2021. https://clinicaltrials.gov/
3. Data on file, Gatehouse Bio; 2021.
4. The ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57-74.