Lee, Sungjin Kim, Young-Youb Ahn, Hyung Jun 2024-01-19T15:00:30Z 2024-01-19T15:00:30Z 2021-09-05 2021-05 0142-9612 https://pubs.kist.re.kr/handle/201004/117080 Therapeutic application of CRISPR/Cas9 nucleases remains a challenge due to the lack of efficient in vivo delivery carriers. Here, we examine the ability of lentiviral vectors pseudotyped with hepatitis C virus (HCV)/E1E2 envelope glycoproteins to systemically deliver CRISPR/Cas9 to hepatic tumors in vivo. We demonstrated that systemic administration of E1E2-pseudotyped lentiviral vectors can selectively deliver Cas9 and sgRNA specific for kinesin spindle protein (KSP) to Huh7 tumors in the orthotopic Huh7 mice due to the specific interactions between E1E2 and their cellular receptors. This specific delivery leads to effective KSP gene disruption, potently inhibiting tumor growth. Furthermore, we demonstrated that E1E2-pseudotyping is more suitable for systemic delivery of CRISPR/Cas9 in cancer therapy than vesicular stomatitis virus-pseudotyping, the most widely used pseudotyping, because of stability in human serum, little transduction to DCs, low innate immune response, and cell-specific targeting ability. This study suggests that E1E2-pseudotyped lentivirus carrying CRISPR/Cas9 can substantially benefit the treatment of Huh7 tumors. English ELSEVIER SCI LTD EFFICIENT GENE-TRANSFER ROSS-RIVER-VIRUS C-VIRUS RETROVIRAL VECTORS CELL ENTRY RECEPTOR DNA PSEUDOPARTICLES GLYCOPROTEINS CRISPR-CAS9 Systemic delivery of CRISPR/Cas9 to hepatic tumors for cancer treatment using altered tropism of lentiviral vector Article 10.1016/j.biomaterials.2021.120793 1 BIOMATERIALS, v.272 BIOMATERIALS 272 scie scopus 000642472700002 2-s2.0-85103689685 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article EFFICIENT GENE-TRANSFER ROSS-RIVER-VIRUS C-VIRUS RETROVIRAL VECTORS CELL ENTRY RECEPTOR DNA PSEUDOPARTICLES GLYCOPROTEINS CRISPR-CAS9 Cancer therapy CRISPR Cas9 Viral tropism Hepatocellular carcinoma Tumor-targeting