Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9‐mediated heterozygous knockdown of DNMT1 in the temsirolimus‐sensitive ccRCC (786‐O) cell line was shown to result in a temsirolimus‐resistant phenotype in vitro and in vivo. The gene discussed is DNMT1; the disease is nonpapillary renal cell carcinoma.