Abstract: The present disclosure provides systems, compositions, and methods for simultaneously editing both strands of a double-stranded DNA sequence at a target site to be edited. In some aspects, the systems comprise a first and second prime editor complex, wherein each of the first and second prime editor complexes comprises (1) a prime editor comprising (i) a nucleic acid programmable DNA binding protein (napDNAbp), and (ii) a polypeptide having an RNA-dependent DNA polymerase activity; and (2) a pegRNA comprising a spacer sequence, gRNA core, a DNA synthesis template, and a primer binding site, wherein the DNA synthesis template encodes a desired DNA sequence or a complement thereof, wherein the desired DNA sequence and the complement thereof form a duplex comprising an edited portion which integrates into the target site to be edited. In some aspects, the systems comprise a first, second, third, and fourth prime editor complex, each comprising a prime editor and a PEgRNA.

Abstract: The present disclosure provides systems, compositions, and methods for simultaneously editing both strands of a double-stranded DNA sequence at a target site to be edited. Further provided herein are pharmaceutical compositions, polynucleotides, vectors, cells, and kits for simultaneously editing both strands of a double-stranded DNA sequence.

Abstract: A claw shearing device including a first member and a second member, each having a connecting portion, a handle portion, and a plurality of grooves formed at an end opposite the handle portion. A fastener is provided to pivotably attach the first member to the second member. The device includes first and second detachable shearing elements, configured to be releasably engageable with the plurality of grooves of the first and second members, respectively. The first and the second detachable shearing elements are configured to form an orifice for the insertion of a claw of a pet or an animal, where the maximum diameter of the orifice is no greater than the maximum diameter of an animal's claw as measured from a tip of the claw to the beginning of a quick that is closest to the tip. The device is configured to bring together the shearing elements to cut the claw of the pet or animal at a predetermined length.