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Despite this potential, a profound gap exists in our knowledge of how to subsequently deliver these RNAs into the specific target cells and turn therapeutically active RNAs into practical medicines. An advanced series of interlocked, thermodynamically self\u2010regulated processes that enable the precise assembly of functional synthetic carriers of siRNA to the target cells in vivo was developed. To demonstrate the efficacy of this delivery system, we used it to treat human cytomegalovirus (HCMV) infection in a humanized mouse model. In this study, we use small interfering RNA (siRNA) and small complementary RNA (scRNA) to inhibit the expressions of two HCMV genes, IE1 and IE2. The auto\u2010regulated nanocarrier polywraplex with core\u2010shell structure was designed to condense and package these RNAs for delivering. To allow these particles recognize the HCMV\u2010infected cells, a ligand was coupled on the surface of nanoparticle, which would specifically target the HCMV\u2010encoded CX<jats:sub>3<\/jats:sub>CL<jats:sub>1<\/jats:sub> chemokine receptor presented in the HCMV\u2010infected cells. The results demonstrated that the polywraplex conjugated with the target molecule CX<jats:sub>3<\/jats:sub>CL<jats:sub>1<\/jats:sub> effectively and specifically delivered the siRNA\/scRNA to HCMV infected cells and inhibited virus growth in vitro and in vivo.<\/jats:p>","DOI":"10.1002\/jmv.28586","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T10:28:42Z","timestamp":1676629722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Rationally designed synthetic vectors for therapeutic nucleic acid delivery against human cytomegalovirus infection"],"prefix":"10.1002","volume":"95","author":[{"given":"Xuemei","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School Rutgers The State University of New Jersey Newark New Jersey USA"},{"name":"Department of Food Science and Technology, College of 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