“Turning tomorrow’s cancer into today’s signal”
A dual-input RNA logic system for precise detection and treatment of HBV-driven liver cancer.
830,000+
Hepatocellular Carcinoma patient deaths in 2020
3rd
Leading cause of cancer death worldwide
50%
of HCC cases from chronic Hepatitis-B
300M+
Global cases of chronic HBV
88%
Recurrence rate even after curative-intent treatment
~30%
5-year survival rate
of recurrence
of recurrence
>90%
Hepatocytes have integrated HBV genome in HCC
Endogenous HCC (GPC3, AKR1B10, and RP11) biomarkers exhibit high expression but insufficient tumor selectivity
Nevertheless, even after developing a vaccine for Hepatitis B, reliable chronic Hepatitis B induced Hepatocellular Carcinoma diagnosis and treatment remain as unsolved challenges.
?
Introducing LiRA, our programmable sensor-therapy actuation system
Click both keys and wait for the safe to activate
LiRA is an AND-gated biosensor that selectively targets cancerous hepatocytes by using transcriptomic signatures to directly bind RNA
Think of LiRA as a lamp with two plugs: unless both inputs are present, the switch will not turn on
The first half of the AND gate targets viral RNA,
while the second half targets an endogenous RNA that is differentially expressed in HCC.
Our AND-gate narrows detection to the overlap between chronic infection and cancer,
minimizing
targeting healthy tissue and providing an alternative to the current standard of care for the millions of lives
affected by HCC.
This is RADAR:
RNA sensing via Adenosine Deaminases Acting on RNA
RADAR converts the presence of target RNA sequences into a functional protein output through adenosine-to-inosine (A→I) editing
In LiRA, each RADAR sensor binds to its target transcript to form double-stranded RNA, recruits ADAR for A to I editing, and initiates translation of a therapeutic peptide.
Together for the first time,
we can leverage the transcriptome to bypass the limits of nonspecific biomarker-based therapies.
Introducing LiRA:
Our programmable sensor-therapy actuation system
An AND-gated biosensor that selectively targets cancerous hepatocytes by using transcriptomic signatures to directly bind RNA
AND
OUT
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