CRISPR needs optimization and delivery reagents. CRISPR is well known to have a lot of off target effects (Unexpected mutations after CRISPR-Cas9 editing in vivo; Nature Methods 14, 547-548, 2017). AUMsilence ASOs can be self-delivered without the use of any delivery agent. Further, AUMsilence ASOs are made of next generation chemical modifications that enhances chemical and intracellular stability, as well as binding to the target RNA, forming very stable heteroduplex structures. Unlike conventional technologies, AUMsilence oligos provides high fidelity for the RNA target and highly reduced off target effects (no RISC associated off target effects).