PT  - JOURNAL ARTICLE
AU  - McCann, Jennifer L
AU  - Salamango, Daniel J
AU  - Law, Emily K
AU  - Brown, William L
AU  - Harris, Reuben S
TI  - MagnEdit—interacting factors that recruit DNA-editing enzymes to single base targets
AID  - 10.26508/lsa.201900606
DP  - 2020 Apr 01
TA  - Life Science Alliance
PG  - e201900606
VI  - 3
IP  - 4
4099  - https://www.life-science-alliance.org/content/3/4/e201900606.short
4100  - https://www.life-science-alliance.org/content/3/4/e201900606.full
SO  - Life Sci. Alliance2020 Apr 01; 3
AB  - Although CRISPR/Cas9 technology has created a renaissance in genome engineering, particularly for gene knockout generation, methods to introduce precise single base changes are also highly desirable. The covalent fusion of a DNA-editing enzyme such as APOBEC to a Cas9 nickase complex has heightened hopes for such precision genome engineering. However, current cytosine base editors are prone to undesirable off-target mutations, including, most frequently, target-adjacent mutations. Here, we report a method to “attract” the DNA deaminase, APOBEC3B, to a target cytosine base for specific editing with minimal damage to adjacent cytosine bases. The key to this system is fusing an APOBEC-interacting protein (not APOBEC itself) to Cas9n, which attracts nuclear APOBEC3B transiently to the target site for editing. Several APOBEC3B interactors were tested and one, hnRNPUL1, demonstrated proof-of-concept with successful C-to-T editing of episomal and chromosomal substrates and lower frequencies of target-adjacent events.