PMID- 28893790
OWN - NLM
STAT- MEDLINE
DCOM- 20180703
LR  - 20180703
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 61
IP  - 12
DP  - 2017 Dec
TI  - Combinatorial CRISPR-Cas9 and RNA Interference Attack on HIV-1 DNA and RNA Can
      Lead to Cross-Resistance.
LID - e01486-17 [pii]
LID - 10.1128/AAC.01486-17 [doi]
AB  - Many potent antiviral drugs have been developed against HIV-1, and their combined
      action is usually successful in achieving durable virus suppression in infected
      individuals. This success is based on two effects: additive or even synergistic
      virus inhibition and an increase in the genetic threshold for development of drug
      resistance. More recently, several genetic approaches have been developed to
      attack the HIV-1 genome in a gene therapy setting. We set out to test the
      combinatorial possibilities for a therapy based on the CRISPR-Cas9 and RNA
      interference (RNAi) mechanisms that attack the viral DNA and RNA, respectively.
      When two different sites in the HIV-1 genome were targeted, either with dual
      CRISPR-Cas9 antivirals or with a combination of CRISPR-Cas9 and RNAi antivirals, 
      we observed additive inhibition, much like what was reported for antiviral drugs.
      However, when the same or overlapping viral sequence was attacked by the
      antivirals, rapid escape from a CRISPR-Cas9 antiviral, assisted by the
      error-prone nonhomologous end joining (NHEJ) DNA repair machinery, accelerated
      the development of cross-resistance to the other CRISPR-Cas9 or RNAi antiviral.
      Thus, genetic antiviral approaches can be combined, but overlap should be
      avoided.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Zhao, Na
AU  - Zhao N
AD  - Laboratory of Experimental Virology, Department of Medical Microbiology, Academic
      Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
FAU - Wang, Gang
AU  - Wang G
AD  - Laboratory of Experimental Virology, Department of Medical Microbiology, Academic
      Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
FAU - Das, Atze T
AU  - Das AT
AD  - Laboratory of Experimental Virology, Department of Medical Microbiology, Academic
      Medical Center, University of Amsterdam, Amsterdam, The Netherlands
      a.t.das@amc.uva.nl b.berkhout@amc.uva.nl.
FAU - Berkhout, Ben
AU  - Berkhout B
AD  - Laboratory of Experimental Virology, Department of Medical Microbiology, Academic
      Medical Center, University of Amsterdam, Amsterdam, The Netherlands
      a.t.das@amc.uva.nl b.berkhout@amc.uva.nl.
LA  - eng
PT  - Journal Article
DEP - 20171122
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antiviral Agents)
RN  - 0 (Bacterial Proteins)
RN  - 0 (DNA, Viral)
RN  - 0 (HIV Core Protein p24)
RN  - 0 (RNA, Guide)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (RNA, Viral)
RN  - 0 (p24 protein, Human Immunodeficiency Virus Type 1)
RN  - EC 3.1.- (Cas9 endonuclease Streptococcus pyogenes)
RN  - EC 3.1.- (Endonucleases)
SB  - IM
MH  - Antiviral Agents/chemistry/metabolism
MH  - Bacterial Proteins/genetics/metabolism
MH  - Base Sequence
MH  - *CRISPR-Cas Systems
MH  - Cell Line, Transformed
MH  - DNA, Viral/*antagonists & inhibitors/biosynthesis/genetics
MH  - Drug Resistance, Viral/*genetics
MH  - Endonucleases/genetics/metabolism
MH  - *Gene Expression Regulation, Viral
MH  - *Genome, Viral
MH  - HIV Core Protein p24/antagonists & inhibitors/biosynthesis/genetics
MH  - HIV-1/*genetics/metabolism
MH  - Humans
MH  - Molecular Targeted Therapy
MH  - RNA Interference
MH  - RNA, Guide/genetics/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - RNA, Viral/*antagonists & inhibitors/biosynthesis/genetics
MH  - T-Lymphocytes/virology
MH  - Virus Replication
PMC - PMC5700367
OTO - NOTNLM
OT  - CRISPR-Cas9
OT  - HIV
OT  - HIV-1
OT  - RNA interference
OT  - RNAi
OT  - antiretroviral resistance
OT  - combination therapy
OT  - escape
OT  - resistance
EDAT- 2017/09/13 06:00
MHDA- 2018/07/04 06:00
CRDT- 2017/09/13 06:00
PHST- 2017/07/24 00:00 [received]
PHST- 2017/09/02 00:00 [accepted]
PHST- 2017/09/13 06:00 [pubmed]
PHST- 2018/07/04 06:00 [medline]
PHST- 2017/09/13 06:00 [entrez]
AID - AAC.01486-17 [pii]
AID - 10.1128/AAC.01486-17 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2017 Nov 22;61(12). pii: AAC.01486-17. doi:
      10.1128/AAC.01486-17. Print 2017 Dec.