Tech

Specific Compounds Can Shield RNA from Degradation

Our formulations incorporate carefully selected compounds with unique properties to protect RNA

Ionic Suppressor

Reduce the movement of protons
and ions in solution, lowering
the catalytic potential of water

Masking Agent

Prevent aggregation and reduce
electrostatic interactions that may
promote RNA degradation

Hydration Coordinator

Order water structure and
hydrogen bonding network of
water molecules around RNA

Molecular Restraint

Restrict RNA movement in solution
and limit flexibility
to prevent self-cleavage

Base Coupler

Interact with bases at hydrophobic
hydrophilic interface to protect
from chemical modifications

Molecular Chaperone

Protect free strands and
unfolded regions that
are more prone to hydrolysis

Combining these compounds produces great synergies and dramatically improves RNA & LNP stability

Want to know how?

Let's use an Ionic Suppressor as an example.

How water catalyzes RNA hydrolysis in solution

Water contributes to proton movement that catalyzes RNA strand cleavage
Suppressing water's ability to donate and exchange protons makes RNA degradation less likely

Mechanism of water catalyzed RNA hydrolysis

Water acting as a base (i.e. hydroxide) starts the hydrolysis reaction by extracting H+ from the 2'OH group.

This forms an unstable intermediate. Protonated water (i.e. hydronium) can then donate a proton back to phosphate, but this time on the 5’-end

Collapse of the intermediate leads to irreversible strand cleavage and a 2’,3’-cyclic phosphate on one end

The 2’,3’-cyclic phosphate hydrolyzes to form a mixture of both 3’ and 2’ phosphate. A hallmark of non-enzymatic RNA hydrolysis

RNA degradation is largely driven by heat (aka energy) and entropy

This is a reason why storing RNA at cold temperatures improves shelf-life and stability

RNA Degradation Requires Activation Energy

The environment surrounding RNA can improve stability by requiring more energy to activate degradation

Storing RNA in formulations that increase the activation energy required to drive degradation can dramatically improve RNA stability and allow storage at higher temperatures

Engineering the Environment
to Increase Activation Energy

Stabilizing Compounds Create Incredible Synergies

Combining multiple compounds with complementary properties can even further improve stability

Mixing an Ionic Suppressor with a Masking Agent improves stability beyond any single compound alone

The combination of both stabilizing compounds displays excellent stability under extreme storage at 60°C for 6 days!

RNA Stored at 60°C for 6 days