Excision of Latent HIV-1 from Infected Cells In Vivo: An Important Step Forward

Feelixge, Harshana S. De Silva; Jerome, Keith R.

doi:10.1016/j.ymthe.2017.04.009

Cited by 2 publications

(3 citation statements)

References 14 publications

(28 reference statements)

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“…Based on this, some authors have demonstrated the feasibility and efficacy of HIV-1 eradication in vivo . Kaminski et al [65] performed experiments on Tg26 transgenic mice, which contain samples corresponding to the HIV-1 virus integrated into their genome, mimicking viral infection [65–67].…”

Section: Crispr-cas To Disrupt Integrated Virus From Animal Modelsmentioning

confidence: 99%

“…These aspects also emphasize that the use of multiplex gRNAs attenuate the chances of generating recombinant viruses with beneficial characteristics [70]. The recent results of provirus excision from live animals open the perspective of conducting human clinical trials in the near future [67, 68].…”

Section: Crispr-cas To Disrupt Integrated Virus From Animal Modelsmentioning

confidence: 99%

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The Potential Use of the CRISPR-Cas System for HIV-1 Gene Therapy

Sanches-da-Silva

Medeiros

Lima

2019

International Journal of Genomics

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The HIV-1 virus (human immunodeficiency virus) affects 36.9 million people worldwide, with approximately 900000 deaths in 2017. The virus carrier can develop severe immunodeficiency since CD4+ T lymphocytes are the main target, leading to acquired immunodeficiency syndrome (AIDS). Despite advances in pharmacological treatment, it is still difficult to eliminate latent reservoirs, becoming one of the main obstacles for viral eradication. The CRISPR- (clustered regularly interspaced short palindromic repeat-) Cas system is a genome-editing method which uses a guide RNA, a complementary sequence to the interested site, recruiting a nuclease that can break the viral or the host cell genetic material. From this double-stranded break, cellular repair mechanisms are activated being able to generate deletions, insertions, or substitutions, in order to inactivate specific gene loci, leading to loss of function. The objective of this minireview is to synthesize the current knowledge on the application of CRISPR-Cas-based gene therapy for HIV-1. The strategies encompass all steps of the viral infection cycle, from inhibition of cell invasion, through viral replication and integration inhibition, to excision of the latent provirus. Off-target effects and ethical implications were also discussed to evaluate the safety of the approach and viability of its application in humans, respectively. Although preclinical and clinical tests are still needed, the recent results establish an exciting possibility of applying this technology for prophylaxis and treatment of HIV-1.

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Section: Crispr-cas To Disrupt Integrated Virus From Animal Modelsmentioning

confidence: 99%

Section: Crispr-cas To Disrupt Integrated Virus From Animal Modelsmentioning

confidence: 99%

The Potential Use of the CRISPR-Cas System for HIV-1 Gene Therapy

Sanches-da-Silva

Medeiros

Lima

2019

International Journal of Genomics

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“…Several laboratories have successfully employed this technology to introduce mutations in the non-coding HIV-1 LTR promoter regions as well as the coding sequences for various viral proteins, causing permanent inactivation of viral gene expression and replication in cell cultures and small animal models. [26–32] Simultaneous use of multiple gRNAs for targeting and editing various regions within the viral genome has led to the removal of large intervening segments of viral DNA and reduces the risk of mutant “escape” virus emerging. [33–35]…”

Section: Reducing the Latent Viral Reservoirmentioning

confidence: 99%

Toward the Cure of HIV-1 Infection: Lessons Learned and Yet to be Learned as New Strategies are Developed

Jacobson

Khalili²

2019

AIDSRev

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More than 10 years have passed since the “Berlin Patient” was presumed to have been cured of his HIV-1 infection when he received allogenic stem cell transplants from a CCR5 Δ32 homozygous donor in addition to chemotherapy and radiation to treat his acute myelocytic leukemia. This event stimulated great hope and a massive research effort toward developing a more generalizable strategy for achieving a cure of HIV-1 infection. Much has been learned, but little therapeutic progress has been made. We review the lessons learned and the challenges that lay ahead for the field, with new potential approaches that can be taken to advance our ability to eliminate active infection in an individual.

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Excision of Latent HIV-1 from Infected Cells In Vivo: An Important Step Forward

Cited by 2 publications

References 14 publications

The Potential Use of the CRISPR-Cas System for HIV-1 Gene Therapy

The Potential Use of the CRISPR-Cas System for HIV-1 Gene Therapy

Toward the Cure of HIV-1 Infection: Lessons Learned and Yet to be Learned as New Strategies are Developed

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