PMID- 26978579
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160316
LR  - 20240325
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 5
IP  - 3
DP  - 2016 Mar 15
TI  - A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus 
      Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA.
PG  - e295
LID - 10.1038/mtna.2016.11 [doi]
AB  - Hepatitis B virus (HBV) infection is a major cause of chronic active hepatitis, 
      cirrhosis, and primary hepatocellular carcinoma, all of which are severe threats 
      to human health. However, current clinical therapies for HBV are limited by 
      potential side effects, toxicity, and drug-resistance. In this study, a 
      cell-penetrating peptide-conjugated peptide nucleic acid (PNA), Tat-PNA-DR, was 
      designed to target the direct repeat (DR) sequences of HBV. Tat-PNA-DR 
      effectively inhibited HBV replication in HepG2.2.15 cells. Its anti-HBV effect 
      relied on the binding of Tat-PNA-DR to the DR, whereby it suppressed the 
      translation of hepatitis B e antigen (HBeAg), HBsAg, HBV core, hepatitis B virus 
      x protein, and HBV reverse transcriptase (RT) and the reverse transcription of 
      the HBV genome. Furthermore, Tat-PNA-DR administered by intravenous injection 
      efficiently cleared HBeAg and HBsAg in an acute hepatitis B mouse model. 
      Importantly, it induced an 80% decline in HBV DNA in mouse serum, which was 
      similar to the effect of the widely used clinical drug Lamivudine (3TC). 
      Additionally, a long-term hydrodynamics HBV mouse model also demonstrated 
      Tat-PNA-DR's antiviral effect. Interestingly, Tat-PNA-DR displayed low 
      cytotoxicity, low mouse acute toxicity, low immunogenicity, and high serum 
      stability. These data indicate that Tat-PNA-DR is a unique PNA and a promising 
      drug candidate against HBV.
FAU - Zeng, Zhengyang
AU  - Zeng Z
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei, People's Republic of China.
FAU - Han, Shisong
AU  - Han S
AD  - Key Laboratory of Biomedical Polymers of Ministry of Education and Department of 
      Chemistry, Wuhan University, Wuhan, Hubei, People's Republic of China.
FAU - Hong, Wei
AU  - Hong W
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei, People's Republic of China.
FAU - Lang, Yange
AU  - Lang Y
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei, People's Republic of China.
FAU - Li, Fangfang
AU  - Li F
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei, People's Republic of China.
FAU - Liu, Yongxiang
AU  - Liu Y
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei, People's Republic of China.
FAU - Li, Zeyong
AU  - Li Z
AD  - Key Laboratory of Biomedical Polymers of Ministry of Education and Department of 
      Chemistry, Wuhan University, Wuhan, Hubei, People's Republic of China.
FAU - Wu, Yingliang
AU  - Wu Y
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei, People's Republic of China.
FAU - Li, Wenxin
AU  - Li W
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei, People's Republic of China.
FAU - Zhang, Xianzheng
AU  - Zhang X
AD  - Key Laboratory of Biomedical Polymers of Ministry of Education and Department of 
      Chemistry, Wuhan University, Wuhan, Hubei, People's Republic of China.
FAU - Cao, Zhijian
AU  - Cao Z
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20160315
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC5014453
EDAT- 2016/03/16 06:00
MHDA- 2016/03/16 06:01
PMCR- 2016/03/01
CRDT- 2016/03/16 06:00
PHST- 2016/01/23 00:00 [received]
PHST- 2016/01/30 00:00 [accepted]
PHST- 2016/03/16 06:00 [entrez]
PHST- 2016/03/16 06:00 [pubmed]
PHST- 2016/03/16 06:01 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - S2162-2531(17)30024-0 [pii]
AID - 10.1038/mtna.2016.11 [doi]
PST - epublish
SO  - Mol Ther Nucleic Acids. 2016 Mar 15;5(3):e295. doi: 10.1038/mtna.2016.11.