Editing proteins inside a cell

Programmable gene editing technologies, such as CRISPR, have increased the capacity to study gene functions and to model diseases. These tools can precisely manipulate DNA and RNA at the nucleotide level in both cellular and whole-animal contexts (1, 2). Proteins constitute another primary class of biomacromolecules that forms the basis of genetic information flow and determines the observable traits of an organism. However, no comparable technique is available for directly editing proteins within a cell. On page 487 of this issue, Beyer et al. (3) report that a pair of split inteins—small protein segments that can undergo a self-sustained protein splicing reaction—enables endogenous protein editing in living mammalian cells. Recently, Hua et al. (4) also reported the manipulation of folded proteins using the split intein–mediated method. Such direct protein editing creates possibilities for introducing previously unachievable protein functions and their spatiotemporal controls at the cellular level.