RNA Biotherapeutics —A New Approach to anOld Problem
Drug development has been focused on
traditional small molecule and protein therapies
for many years, but these approaches haveprovided means to address only a small fractionof desired targets and diseases. Discovery of theRNA interference (RNAi) process opened a newdoor to therapeutics discovery and development.
RNA-based biotherapeutics are on the rise andpositioned to provide a rapid, cost-effective, andreadily adaptable way to address previously“undruggable” targets.
This infographic provides a brief history ofRNA-based therapy and outlines how Bio-Rad™
Droplet Digital™ PCR (ddPCR™) technology
supports this field of work.

The RNA Biotherapeutics Difference

14%

3,624

Percent of the human genome targetable
by traditional drug therapies1

RNA therapeutics publications
released in 20212

Small molecule, protein, and othertraditional approaches to drug discovery
have plateaued in their ability to affectclinically meaningful targets.

The delivery of RNA to cells to affect theexpression of target proteins is a relatively new
approach that holds great promise to target
previously undruggable proteins and changethe standard of care for many diseases. RNAtherapeutics are also relatively fast andcost-effective to develop and are more easily
adaptable than traditional therapies.1

Timeline and Metrics

RNA biotherapeutics are based on the RNAi process that was discovered
less than 25 years ago.

1998

2018

Nature paper3 by Craig Mello and Andrew
Fire is published to first describe RNAi.

2006

Patisiran is the first FDA approved
therapeutic using RNAi.

Craig Mello and Andrew Fire receive The Nobel Prizeand RNAi is recognized as a new opportunity for
drug discovery and development.

While relatively new, RNAi has quickly been recognized as an opportunity
for unique drug development and a pipeline of RNA-based biotherapeutics
has been developed.

Type of RNATOTAL

FDA or EU
Approved(including EUA)

Messenger RNA(mRNA)

2

Antisense
oligonucleotides (ASO)435

In Phase
I/II Trials

RNA-based therapies
approved for use orin current clinical trials1

21

3

MicroRNA (miRNA)

Aptamer (miRNA)

1

Small interfering RNA(siRNA)2

2

New Targets Available
Developers have overcome challenges of using RNA as a therapeutic (e.g.,
avoiding degradation, deliverying across the cell membrane, and managing
immunotoxic cell response)1 to produce RNAi-based drugs to help with thefollowing diseases and conditions:
Cancer

Eye-related disorders

Cardiovascular disease

Renal injury and failure

Viral infections

Hemophilia

ddPCR Technology and Application in RNA Therapeutics
Bio-Rad ddPCR technology provides absolute quantification of RNA andgene expression for low copy number templates.

1
RNA sample withtarget sequenceis partitioned intodroplets

2
Target andbackground RNA
are randomly
distributed among
20,000 droplets

34

Target sequenceis amplified by
end-point PCR ineach droplet

Positive droplets
are counted togive precise
quantification oftarget sequencesin sample

Development, testing, and production of RNA therapeutics is supportedby ddPCR technology in the following ways:
Biomarker discovery

Copy number variant analysis

Rare variant detection

Ratio analysis for multivalent therapies

Gene expression analysis

RNA therapeutic titer

Used to establish a positive correlation between
CRED9 and CEBPA mRNA expression in
multiple cancer cell lines4

Demonstrated to provide sensitivity, accuracy,
reproducibility, and scalability for higher-throughputcapabilities in AAV viral genome titration acrossmultiple transgenes and serotypes5

Poly(A) tail level determination

Biodistribution studies

Cited as a Poly(A) determination method bydeveloper of a commercially available
SARS-CoV-2 mRNA vaccine6

Used for RNA biodistribution studies based onsensitivity, precision, reproducibility, and ability todetect low copy numbers, and reduced interference
form endogenous RNA7

https://www.bio-rad.com/digital-assays/assay-detail/dEXD77548788

Visit bio-rad.com/RNA
https://www.biorad.com/RNA to learn more.

References
1.
2.
3.
4.
5.
6.
7.

DamaseTR etorg/articles/10.
al. (2021).
The2021.
limitlessfuture of RNA therapeutics. Front Bioeng Biotechnol,
https://www.frontiersin.
3389/fbioe.
628137/full?fbclid=IwAR1hf9aSKPggBAqooXTy7HHsEQQpOCNvQ-frY_gTkX5eVpdiYR1bqUc02eU#B73
https://pubmed.ncbi.nlm.nih.gov/
https://www.nature.com/articles/35888
Fire A et al. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391, 806-811.
https://rnajournal.cshlp.org/content/early/2021/05/26/rna.078752.121.full.pdf
Setten RL et al. (2021). CRED9: A differentially expressed elncRNA regulates expression of transcription factor CEBPA. RNA, 8, 891-906.
https://smanewstoday.com/wp-content/uploads/2022/05/PIIS1525001622002465.pdf
Nelson SC et al. (2022). Assessment and comparison of digital PCR platforms for AAV viral genome titer. ASGCT Meeting abstract.
https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf
Vervaeke P et al. (2022). Regulatory guidelines and preclinical tools to study the biodistribution of RNA tharapeutics. Adv Drug Deliv Rev, 184.
https://www.sciencedirect.com/science/article/pii/S0169409X22001260

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