https://scholars.lib.ntu.edu.tw/handle/123456789/568349
標題: | The potential and challenges of CRISPR-Cas in eradication of hepatitis B virus covalently closed circular DNA | 作者: | HUNG-CHIH YANG PEI-JER CHEN |
公開日期: | 2018 | 出版社: | Elsevier B.V. | 卷: | 244 | 起(迄)頁: | 304-310 | 來源出版物: | Virus Research | 摘要: | Current antiviral therapy fails to cure chronic hepatitis B virus (HBV) infection, primarily because of the persistence of covalently closed circular DNA (cccDNA). Although nucleos(t)ide analogues (NAs) can inhibit the reverse transcriptase of HBV and suppress its replication to levels below the detection limit, viremia often rebounds after cessation of therapy. Nuclear cccDNA serves as the HBV replicative template and exhibits extraordinary stability, and is not affected by NAs. Therefore, curing chronic hepatitis B (CHB) requires novel therapy for purging cccDNA from patients. The CRISPR/Cas9 system is a newly developed programmable genome-editing tool and allows for sequence-specific cleavage of DNA. Compared to other genome-editing tools, the CRIPSR/Cas9 system is advantageous for its simplicity and flexibility of design. Theoretically, Cas9 can be redirected to specifically cleave any desired genome sequences simply by designing guide RNAs with about 20 nucleotides that match the particular sequences of genomes with downstream protospacer adjacent motifs. Recently, it has been demonstrated that the CRIPSR/Cas9 system can specifically destruct HBV genomes in vitro and in vivo. Although promising, the CRISPR/Cas9 system faces several challenges that need to be overcome for the clinical application, namely, off-target cleavage and the in vivo delivery efficiency. Cutting integrated HBV genomes by CRISPR/Cas9 also raises serious concern because this has the risk of genome instability. In summary, the CRISPR/Cas9 system bears the potential for curing CHB as long as several challenging issues can be successfully solved. ? 2017 |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021103807&doi=10.1016%2fj.virusres.2017.06.010&partnerID=40&md5=31c22d376998d2284a733d010215be0b https://scholars.lib.ntu.edu.tw/handle/123456789/568349 |
ISSN: | 0168-1702 | DOI: | 10.1016/j.virusres.2017.06.010 | SDG/關鍵字: | alpha interferon; circular DNA; bacterial protein; Cas9 endonuclease Streptococcus pyogenes; circular DNA; endonuclease; guide RNA; virus DNA; antiviral therapy; chronic hepatitis B; CRISPR-CAS9 system; gene editing; Hepatitis B virus; human; nonhuman; priority journal; Review; viral clearance; virus genome; virus inactivation; chronic hepatitis B; clustered regularly interspaced short palindromic repeat; CRISPR Cas system; DNA cleavage; genetics; genomic instability; growth, development and aging; Hepatitis B virus; metabolism; molecularly targeted therapy; patient safety; procedures; virology; virus replication; Bacterial Proteins; Clustered Regularly Interspaced Short Palindromic Repeats; CRISPR-Cas Systems; DNA Cleavage; DNA, Circular; DNA, Viral; Endonucleases; Genomic Instability; Hepatitis B virus; Hepatitis B, Chronic; Humans; Molecular Targeted Therapy; Patient Safety; RNA, Guide; Virus Replication |
顯示於: | 臨床醫學研究所 |
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