We screen CLANs both in vitro and in vivo and select a preferable CLAN to deliver mCas9/gNLRP3 into macrophages, which ameliorates LPS-induced septic shock, MSU-induced peritonitis and HFD-induced T2D by disrupting NLRP3 in macrophages. Here, NLRP3 is linked to type 2 diabetes mellitus.