A Combinatorial CRISPR-Cas9 Attack on HIV-1 DNA Extinguishes All Infectious Provirus in Infected T Cell Cultures

Wang, Gang; Zhao, Na; Berkhout, Ben; Das, Atze T.

doi:10.1016/j.celrep.2016.11.057

Cited by 116 publications

(178 citation statements)

References 25 publications

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“…For instance, sgRNAs targeting the coding sequences of plant geminiviruses led to frequent viral escapes; however, no viral escape was identified with sgRNAs targeting the noncoding intergenic region, which is essential for replication (Ali, Ali, Tashkandi, Zaidi, & Mahfouz, ). This is different from what has been previously reported regarding the Cas9‐mediated resistance to HIV (Wang, Pan, et al., ; Wang, Zhao, Berkhout, & Das, 2016a; Wang et al., 2016b). Escaped HIV mutants have been generated in Cas9‐expressing cells and single sgRNAs targeting either coding sequences or noncoding long terminal repeats (LTRs).…”

Section: Resultscontrasting

confidence: 98%

CRISPR/Cas9‐mediated resistance to cauliflower mosaic virus

Liu

Soyars

et al. 2018

Plant Direct

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Viral diseases are a leading cause of worldwide yield losses in crop production. Breeding of resistance genes ( R gene) into elite crop cultivars has been the standard and most cost‐effective practice. However, R gene‐mediated resistance is limited by the available R genes within genetic resources and in many cases, by strain specificity. Therefore, it is important to generate new and broad‐spectrum antiviral strategies. The CRISPR ‐Cas9 (clustered regularly interspaced palindromic repeat, CRISPR ‐associated) editing system has been employed to confer resistance to human viruses and several plant single‐stranded DNA geminiviruses, pointing out the possible application of the CRISPR ‐Cas9 system for virus control. Here, we demonstrate that strong viral resistance to cauliflower mosaic virus (Ca MV ), a pararetrovirus with a double‐stranded DNA genome, can be achieved through Cas9‐mediated multiplex targeting of the viral coat protein sequence. We further show that small interfering RNA s (si RNA ) are produced and mostly map to the 3′ end of single‐guide RNA s (sg RNA ), although very low levels of si RNA s map to the spacer region as well. However, these si RNA s are not responsible for the inhibited Ca MV infection because there is no resistance if Cas9 is not present. We have also observed edited viruses in systematically infected leaves in some transgenic plants, with short deletions or insertions consistent with Cas9‐induced DNA breaks at the sg RNA target sites in coat protein coding sequence. These edited coat proteins, in most cases, led to earlier translation stop and thus, nonfunctional coat proteins. We also recovered wild‐type CP sequence in these infected transgenic plants, suggesting these edited viral genomes were packaged by wild‐type coat proteins. Our data demonstrate that the CRISPR ‐Cas9 system can be used for virus control against plant pararetroviruses with further modifications.

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Section: Resultscontrasting

confidence: 98%

CRISPR/Cas9‐mediated resistance to cauliflower mosaic virus

Liu

Soyars

et al. 2018

Plant Direct

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“…Using the CRISPRCas9 system in combination with two antiviral gRNAs the blocking of viral replication could be attained [39]. Another disease to which this system brings therapeutic value is hepatitis B; knowing that the mini-chromosomal cccDNA (covalently closed circular DNA) generates a new viral antigen, the editing tool could be used to remove cccDNA which would lead to lower HBsAg levels [40].…”

Section: Biotechnology Engineering and Applications In Pharmacologymentioning

confidence: 99%

Review. Development, Applications, Benefits, Challenges and Limitations of the New Genome Engineering Technique. An Update Study

Crauciuc

Tripon

Gheorghiu

et al. 2017

Acta Medica Marisiensis

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We assume that the CRISPR Cas9 theory must be delimited by applicability, because the consequences of long term DNA manipulation remain unknown. Moreover, the irreversibility of this procedure should instigate researchers to reserved opinions. Usefulness as well as benefits of CRISPR Cas9 made it one of the most popular and used genome editing technique. But with its huge potential, ethical and safety concerns emerge. Therefore, before continuing research in this direction we should have a well organized system that is able to make that differentiation between research and reproduction. However we truly believe in the future of genetic engineering and with the CRISPR-Cas9 system we expect that the opportunity of treating now so called incurable diseases arises. Time is all we need.

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“…Triple combination of 10 gRNAs suggested the accessibility of multitargeted intensive sites [34]. Recently, researchers combined two antiviral gRNAs which targeted different regions of HIV-1 genome and demonstrated the prevention of viral escape and powerful inhibition of HIV replication [35,36]. Provirus deletion in latency could get rid of the risk of viral rebound, and the prospect is promising when several gRNAs are combined.…”

Section: Excising the Provirusmentioning

confidence: 99%

CRISPRs encounter Cocktail: a dawn for curing HIV/AIDS

Li¹,

Zhang²,

Feng³

et al. 2017

Virol Res Rev

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a These authors contributed equally to this work. AbstractThe acquired immunodeficiency syndrome (AIDS) patients can scarcely be cured completely because of the Human Immunodeficiency Virus (HIV) provirus existence post-infection in body, though cocktail of the highly active antiretroviral therapy (HAART) has achieved great effects on controlling and decreasing HIV clinically. Recently, the genome editing strategies are developing by leaps and bounds. Among three generation of technologies, the clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein 9 (Cas9) is a newborn to former zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) but grows fast into the most popular at present, because of its advantages in less time-and cost-consuming. Eradicating HIV by disrupting the viral co-receptor C-C chemokine receptor type five (CCR5) or C-X-C chemokine receptor type four (CXCR4) gene, excising the provirus segments integrated into human genome, or activating/inactivating the replication of the virus genome by using these technologies are several current strategies to reach the goal of AIDS prevention and treatment. It seems hard, however, to arrive the keen anticipation exactly by using them respectively. After a comprehensive literature review, it concluded that the combination of those interventions, as together co-receptor with provirus genome interference as a cocktail edition, may lead us to an eventual cure for the horrible disease.

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A Combinatorial CRISPR-Cas9 Attack on HIV-1 DNA Extinguishes All Infectious Provirus in Infected T Cell Cultures

Cited by 116 publications

References 25 publications

CRISPR/Cas9‐mediated resistance to cauliflower mosaic virus

CRISPR/Cas9‐mediated resistance to cauliflower mosaic virus

Review. Development, Applications, Benefits, Challenges and Limitations of the New Genome Engineering Technique. An Update Study

CRISPRs encounter Cocktail: a dawn for curing HIV/AIDS

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