Jason Stephany

ARTICLE Reviewing Editor: Carol Beth Post This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/pro.4656. Abstract Hsp90 is a molecular chaperone involved in the refolding and activation of numerous protein substrates referred to as clients.

Abstract CRISPR/Cas9 nucleases are powerful genome engineering tools, but unwanted cleavage at off-target and previously edited sites remains a major concern. Numerous strategies to reduce unwanted cleavage have been devised, but all are imperfect. Here, we report off-target sites can be shielded from the active Cas9•single guide RNA (sgRNA) complex through the co-administration of dead-RNAs (dRNAs), truncated guide RNAs that direct Cas9 binding but not cleavage.

a, Illustrative examples of variant abundance classifications, with the dotted line representing the threshold above which 95% of synonymous variants reside. Points represent the VAMP-seq score for each representative variant, with error bars denoting the 95% confidence interval derived from experimental replicates. n values are 3, 5, 2, and 4 for p.Thr2Asp, p.Thr5Ala, p.Glu7His, and Lys6Ile, respectively.