I am not a biologist, but nevertheless I found out something interesting today regarding the problem of designing good guide RNA via machine learning.
The work that I learnt about today addresses 2 key questions via machine learning approaches: off-target effects of CRISPR (http://biorxiv.org/content/early/2016/10/05/078253) and optimization of the guide RNA sequence to maximize on-target activity and minimize off target effects (http://www.nature.com/nbt/journal/v34/n2/full/nbt.3437.html).
I learnt of this stuff from one of the authors who works at MSR New England (http://nicolofusi.com/).
Also of possible interest is their project page https://www.microsoft.com/en-us/research/project/crispr/, where they are planning to release a cloud-based service for end-to-end guide design by incorporating the approaches developed in the above work.