Moving from in vitro to in vivo CRISPR screens

Clustered regularly interspaced short palindromic repeats (CRISPR) screens emerged as the gold standard technology in genetic screening in recent years. Most CRISPR screens are conducted in vitro, although current technologies fail to completely recapitulate the in vivo physiological environment. Direct in vivo screening - where cells are targeted within their natural niche - is emerging as a powerful approach to unravel biological processes in intact tissues and organs, taking into account complex cellular interactions, immune response, extracellular matrix, and tissue architecture. Several recent studies have demonstrated the capacity of in vivo screens to identify unique genetic dependencies left uncovered by in vitro screens. Together with new single cell readout techniques, in vivo CRISPR screens will continue to fuel progress towards identifying genetic elements controlling development, health, and disease.