New CRISPR Vehicles

In Nature we have an article demonstrating a variant on the now standard CRISPR cas9 vehicle. As they first note:

Type II CRISPR-Cas systems require only two main components for eukaryotic genome editing: a Cas9 enzyme, and a chimaeric sgRNAderived from the CRISPR RNA (crRNA) and the noncoding trans-activating crRNA (tracrRNA). Analysis of over 600 Cas9 orthologues shows that these enzymes are clustered into two length groups with characteristic protein sizes of approximately 1,350 and 1,000 amino acid residues, respectively

Thus the classic source is  Streptococcus pyogenes and as noted:

The RNA-guided endonuclease Cas9 has emerged as a versatile genome-editing platform. However, the size of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for basic research and therapeutic applications that use the highly versatile adeno-associated virus (AAV) delivery vehicle. 

But the same vehicle with a Cas9 is in many other bacteria and they note:

 Here, we characterize six smaller Cas9 orthologues and show that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of SpCas9, while being more than 1 kilobase shorter. We packaged SaCas9 and its single guide RNA expression cassette into a single AAV vector and targeted the cholesterol regulatory gene Pcsk9 in the mouse liver.

Thus we have a variant but the same functionality. They conclude regarding in vivo changes:

Here, we develop a small and efficient Cas9 from S. aureus for in vivo genome editing. The results of these experiments highlight the power of using comparative genomic analysis in expanding the CRISPR-Cas9 toolbox. Identification of new Cas9 orthologues, in addition to structure-guided engineering, could yield a repertoire of Cas9 variants with expanded capabilities and minimized molecular weight, for nucleic acid manipulation to further advance genome and epigenome engineering. ...We examined these sites in liver tissue transduced by AAV-SaCas9 and did not observe any indel formation within the detection limits of in vitro BLESS and targeted deep sequencing. Importantly, the off-target sites identified in vitro might differ from those in vivo, which need to be further evaluated by the applications of BLESS or other unbiased techniques such as those published during the revision of this work. Finally, we did not observe any overt signs of acute toxicity in mice at one to four weeks after virus administration. ....these findings suggest that in vivo genome editing using SaCas9 has the potential to be highly efficient and specific.

 This an an interesting next step.