A new genetic screening platform that uses CRISPR-Cas13 has been used to target thousands of genes in a massively parallel fashion, and to reveal the principals for guide RNA design. These principals may now expedite the accurate design of optimized guide RNAs for detecting, targeting, and knocking down specific RNA targets. Also, a critical “seed” region has been identified that is exquisitely sensitive to mismatches between the CRISPR guide and the target.