Small RNAs in drug development

Fastest growing area of research

4x

growth in sRNA focused publications over the last decade1

3%

of clinical trials in 2020 used sRNA2

34

RNA drugs in active clinical trials3

12

FDA Approved RNA 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 mutations drive disease3

SMALL RNA ARE MASTER REGULATORS OF GENE EXPRESSION FOUND IN BLOOD AN D TISSUE

sRNA

Small RNAs control every biological pathway and process

Deregulation of small RNAs causes and drives diseases

Unique expression patterns in tissues and cell types enable classification

Present in every matrix

Easily extracted and very stable in samples

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

MUTATIONS IN POST TRANSCRIPTIONAL PROCESSING OF SMALL RNAs DRIVE DISEASE BY DISRUPTING PROTEIN EXPRESSION

sRNA_isoform_variability
Small RNA analysis requires single nucleotide fidelity

'Seed' sequence – directs RISC to target site RNA

Mutations that shift the 'Seed' sequence causing regulation of the wrong proteins
Current data processing and annotation methods condense and obscure the sRNA mutations that drive disease.

NEXT: Check out our pipeline

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.