期刊
BIOMATERIALS
卷 272, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.120793
关键词
Cancer therapy; CRISPR; Cas9; Viral tropism; Hepatocellular carcinoma; Tumor-targeting
资金
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [2016R1A2B3006644]
- KIST institutional Program [2E30350]
- National Research Foundation of Korea [2016R1A2B3006644] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The study demonstrated successful systemic delivery of CRISPR/Cas9 to Huh7 tumors using lentiviral vectors pseudotyped with hepatitis C virus glycoproteins, effectively inhibiting tumor growth. E1E2-pseudotyping proved to be superior for cancer therapy compared to vesicular stomatitis virus-pseudotyping due to stability, low immune response, and cell-specific targeting.
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.
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