A brief description of the principle of CRISPR:

Full name: Clustered regularly interspaced short palindromic repeats

Biological origin

The RNA-programmable Cas9 endonuclease cleaves double-stranded DNA at sites complementary to a 20-base-pair guide RNA. The Cas9 system has been used to modify genomes in multiple cells and organisms, demonstrating its potential as a facile genome engineering tool. However, As viruses evolve in response to the selective pressure induced by the CRISPR-Cas immune system, the host is in turn under pressure to attack slightly mutated target sequences in addition to the target. It is therefore not surprising that Cas nucleases exhibit considerable off-target activity on sequences like the intended target. Such off-targeting presents a severe problem for therapeutics, as DNA breaks introduced at the wrong site could lead to loss-of-function mutations in a well-functioning gene or the improper repair of a disease-causing gene.

Why we model?

Off-target has always been a nightmare for the experimentalists. Lure has sequences similar to the target, whose existence can extremely affect the probability of sucess. Therefore, to find the lure sequences and pick our the target sequence with high probability of off-target is a vital work.
However, our modelers can provide such information to the experimentalists. Based on the simulation, we can find the numbers and locations of lure sequences and give coresponding intructions to the project. Then, much unnesessary work can be avoided.

Target Recognition Model

How to explain the cleavage probability?

the RGN initially binds its substrate at the PAM site, from which it can either unbind with rate $ k_b(0) $ or initiate R-loop formation with rate $ k_f(0) $. A partially formed R-loop of length n grows to length n+1 with rate $ k_f(n) $ or shrinks to length n-1 with rate $ k_b(n) $. Eventually, the RGN will either cleave its substrate with rate $ k_f(N) $ or reject the substrate and unbind with rate $ k_b(0) $.