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In particular with the CRISPRa approach, the transcriptional activators that are fused to the dCas9 enzyme will increase the length of the construct, such that a combination of sgRNA and dCas9-transcriptional activators will be too large to load onto a single AAV vector

United European Gastroenterol J 9:781786

"A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy." Oncologist 18(11): 1190-1191

FDA stated it lacked safety-related information for certain other injectable routes, meaning the agency did not have enough information to determine whether harm would occur through those routes