Abstract: The present disclosure provides a composition comprising a solid support, a plurality of tethered oligonucleotides attached to the solid support, and a plurality of untethered oligonucleotides hybridized to the tethered oligonucleotides. An untethered oligonucleotide can comprise, attached via the 5? end, a cell, or an effector molecule. Hybridization of an untethered oligonucleotide to a tethered oligonucleotide generates an enzyme cleavage site, which allows for temporally controlled removal of an effector molecule. The present disclosure provides methods of temporally modulating the activity and/or phenotype of a cell. The present disclosure provides a solid support comprising patterned tethered oligonucleotides attached thereto; and methods of making the solid support.

Abstract: The present disclosure provides variant CRISPR-Cas effector polypeptides, as well as engineered guide nucleic acids, and systems comprising the same. The present disclosure provides methods of modifying a target nucleic acid, using a variant CRISPR-Cas effector polypeptide of the present disclosure.