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Here, we identify ~140-aa miniature deaminase inhibitors (Sddis) that bind cognate single-stranded DNA deaminases (Sdds) with high affinity and specificity, occluding their DNA-binding surfaces to completely inhibit C-to-T activity. Based on these inhibitors, we engineer an adenine and cytosine base editing-regulated transformation system (ACBE-RTS). This platform features two inactive dSdds fused to nCas9 as docking arms, with effector modules provided by doxycycline-inducible SviSddi\u2013SflSdd (CBE) and cumate-inducible Air1Sddi\u2013ABE8e (ABE) fusions. Small-molecule regulation enables switching among four modes (OFF, CBE, ABE, ACBE), achieving up to 43.4% C-to-T or 42.9% A-to-G editing at four endogenous human sites. Using a 4000-member sgRNA library in MARC-145 cells stably expressing ACBE-RTS, a three-round screening identified four key amino acids in monkey CD163 that reduced replication of highly pathogenic PRRSV by &amp;gt;100-fold and eliminated detectable viral-antigen staining. Compact and multi-mode switchable on a single Cas9 scaffold, ACBE-RTS establishes a versatile framework for precision therapeutics and genetic interrogation. Its modular Sddi\u2013Sdd interface could in principle be readily extended to other base editors, such as thymine and guanine base editors (TBE and GBE).<\/jats:p>","DOI":"10.1093\/nar\/gkag162","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T09:29:30Z","timestamp":1774862970000},"source":"Crossref","is-referenced-by-count":0,"title":["Regulated transformation system (RTS): sddi-mediated programmable shut-off and mode switching of base editors"],"prefix":"10.1093","volume":"54","author":[{"given":"Jiacheng","family":"Deng","sequence":"first","affiliation":[{"name":"College of Animal Sciences, Jilin University , Changchun 130062 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Jilin University , Changchun 130062 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,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daxin","family":"Pang","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Jilin University , Changchun 130062 ,","place":["China"]},{"name":"Chongqing Research Institute, Jilin University , Chongqing 401123 ,","place":["China"]},{"name":"Chongqing Jitang Biotechnology Research Institute , Chongqing 401123 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Jilin University , Changchun 130062 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0809-5599","authenticated-orcid":false,"given":"Hongming","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Jilin University , Changchun 130062 ,","place":["China"]},{"name":"Chongqing Research Institute, 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