In vivo CRISPR editing with no detectable genome-wide off-target mutations.

CRISPR-Cas genome-editing nucleases hold substantial promise for developing human therapeutic applications but identifying unwanted off-target mutations is important for clinical translation. A well-validated method that can reliably identify off-targets in vivo has not been described to date, which means it is currently unclear whether and how frequently these mutations occur. Here we describe 'verification of in vivo off-targets' (VIVO), a highly sensitive strategy that can robustly identify the genome-wide off-target effects of CRISPR-Cas nucleases in vivo.

RNA Interference (RNAi)-Based Therapeutics: Delivering on the Promise?

A resurgence in clinical trials using RNA interference (RNAi) occurred in 2012. Although there were initial difficulties in achieving efficacious results with RNAi without toxic side effects, advances in delivery and improved chemistry made this resurgence possible. More than 20 RNAi-based therapeutics are currently in clinical trials, and several of these are Phase III trials.

RNA interference approaches for treatment of HIV-1 infection.

HIV/AIDS is a chronic and debilitating disease that cannot be cured with current antiretroviral drugs. While combinatorial antiretroviral therapy (cART) can potently suppress HIV-1 replication and delay the onset of AIDS, viral mutagenesis often leads to viral escape from multiple drugs. In addition to the pharmacological agents that comprise cART drug cocktails, new biological therapeutics are reaching the clinic.

Current progress of RNA aptamer-based therapeutics.

Aptamers are single-stranded nucleic acids that specifically recognize and bind tightly to their cognate targets due to their stable three-dimensional structure. Nucleic acid aptamers have been developed for various applications, including diagnostics, molecular imaging, biomarker discovery, target validation, therapeutics, and drug delivery. Due to their high specificity and binding affinity, aptamers directly block or interrupt the functions of target proteins making them promising therapeutic agents for the treatment of human maladies.