Zinc-Finger Nucleases Induced by HIV-1 Tat Excise HIV-1 from the Host Genome in Infected and Latently Infected Cells

Ji, Haiyan; Lu, Panpan; Liu, Baochi; Qu, Xin; Wang, Yanan; Jiang, Zhen; Yang, Xinyi; Zhong, Yangcheng; Yang, Haiwei; Pan, Hongda; Zhao, Lin; Xu, Jianqing; Lu, Hongzhou; Zhu, Huanzhang

doi:10.1016/j.omtn.2018.04.014

Cited by 16 publications

(14 citation statements)

References 35 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The biotechnology is restricted in terms of attachment with 3 codons on either side of the DNA chain. The technique in recent years has gained widespread popularity due to its simplicity and specificity, and it is being employed in clinical usage for certain diseases 17, 18Figure 4Schematic Showing Step by Step Zinc-Finger Nuclease-Induced Genome EditingThe mechanisms include the following: (1) ZFNs containing FokI endonucleases and protein-binding domains are introduced into the cell, (2) FokI and protein-binding domains are released to enter the nucleus, (3) protein-binding domains attach with DNA fragment to be removed, (3) FokI cuts out the identified DNA segment by creating double-stranded DNA break, and (4) the desirable DNA segment is inserted and integrated into the DNA sequence.TALENs.…”

Section: Main Textmentioning

confidence: 99%

Genome-Editing Technologies: Concept, Pros, and Cons of Various Genome-Editing Techniques and Bioethical Concerns for Clinical Application

Khan

2019

Molecular Therapy - Nucleic Acids

172

View full text Add to dashboard Cite

The traditional healthcare system is at the doorstep for entering into the arena of molecular medicine. The enormous knowledge and ongoing research have now been able to demonstrate methodologies that can alter DNA coding. The techniques used to edit or change the genome evolved from the earlier attempts like nuclease technologies, homing endonucleases, and certain chemical methods. Molecular techniques like meganuclease, transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs) initially emerged as genome-editing technologies. These initial technologies suffer from lower specificity due to their off-targets side effects. Moreover, from biotechnology's perspective, the main obstacle was to develop simple but effective delivery methods for host cell entry. Later, small RNAs, including microRNA (miRNA) and small interfering RNA (siRNA), have been widely adopted in the research laboratories to replace lab animals and cell lines. The latest discovery of CRISPR/Cas9 technology seems more encouraging by providing better efficiency, feasibility, and multi-role clinical application. This later biotechnology seem to take genomeengineering techniques to the next level of molecular engineering. This review generally discusses the various gene-editing technologies in terms of the mechanisms of action, advantages, and side effects.

show abstract

Section: Main Textmentioning

confidence: 99%

Genome-Editing Technologies: Concept, Pros, and Cons of Various Genome-Editing Techniques and Bioethical Concerns for Clinical Application

Khan

2019

Molecular Therapy - Nucleic Acids

172

View full text Add to dashboard Cite

show abstract

“…A number of studies have utilized engineered ZFPs to target HIV proviruses. For example, ZFPs have been fused with nucleases [185][186][187] and transcriptional repressors [188][189][190][191][192] or activators [193], and tested in HIV-1 reporter cell lines and cell line models of HIV-1 latency, as well as primary human peripheral blood mononuclear cells [185,188,190].…”

Section: Zinc Finger Proteinsmentioning

confidence: 99%

Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy

Schwarzer

Gramatica

Greene

2020

Viruses

View full text Add to dashboard Cite

Human immunodeficiency virus (HIV-1) indefinitely persists, despite effective antiretroviral therapy (ART), within a small pool of latently infected cells. These cells often display markers of immunologic memory and harbor both replication-competent and -incompetent proviruses at approximately a 1:100 ratio. Although complete HIV eradication is a highly desirable goal, this likely represents a bridge too far for our current and foreseeable technologies. A more tractable goal involves engineering a sustained viral remission in the absence of ART--a "functional cure." In this setting, HIV remains detectable during remission, but the size of the reservoir is small and the residual virus is effectively controlled by an engineered immune response or other intervention. Biological precedence for such an approach is found in the post-treatment controllers (PTCs), a rare group of HIV-infected individuals who, following ART withdrawal, do not experience viral rebound. PTCs are characterized by a small reservoir, greatly reduced inflammation, and the presence of a poorly understood immune response that limits viral rebound. Our goal is to devise a safe and effective means for replicating durable post-treatment control on a global scale. This requires devising methods to reduce the size of the reservoir and to control replication of this residual virus. In the following sections, we will review many of the approaches and tools that likely will be important for implementing such a "reduce and control" strategy and for achieving a PTC-like sustained HIV remission in the absence of ART.

show abstract

“…Elimination of proviral DNA from latently infected viral reservoirs has potentially curative implications. Gene editing using ZFNs [107,108] and TALENs [109,110] have already been used to recognise HIV proviral DNA sequences. Similarly, CRISPR/Cas9 is widely being adopted for this purpose, delivered either transiently to inactivate existing HIV provirus, or stably expressed, providing defence towards invading HIV-1.…”

Section: Editing Of the Latent Viral Reservoirmentioning

confidence: 99%

Emerging CRISPR/Cas9 applications for T-cell gene editing

Preece¹,

Georgiadis²

2019

Emerging Topics in Life Sciences

View full text Add to dashboard Cite

Gene editing tools are being rapidly developed, accelerating many areas of cell and gene therapy research. Each successive gene editing technology promises increased efficacy, improved specificity, reduced manufacturing cost and design complexity; all of which are currently epitomised by the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas9) platform. Since its conceptualisation, CRISPR-based gene editing has been applied to existing methodologies and has further allowed the exploration of novel avenues of research. Implementation of CRISPR/Cas9 has been instrumental to recent progress in the treatment of cancer, primary immunodeficiency, and infectious diseases. To this end, T-cell therapies have attempted to harness and redirect antigen recognition function, and through gene editing, broaden T-cell targeting capabilities and enhance their potency. The purpose of this review is to provide insights into emerging applications of CRISPR/Cas9 in T-cell therapies, to briefly address concerns surrounding CRISPR-mediated indel formation, and to introduce CRISPR/Cas9 base editing technologies that hold vast potential for future research and clinical translation.

show abstract

Zinc-Finger Nucleases Induced by HIV-1 Tat Excise HIV-1 from the Host Genome in Infected and Latently Infected Cells

Cited by 16 publications

References 35 publications

Genome-Editing Technologies: Concept, Pros, and Cons of Various Genome-Editing Techniques and Bioethical Concerns for Clinical Application

Genome-Editing Technologies: Concept, Pros, and Cons of Various Genome-Editing Techniques and Bioethical Concerns for Clinical Application

Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy

Emerging CRISPR/Cas9 applications for T-cell gene editing

Contact Info

Product

Resources

About