Application of CRISPR/Cas9-Based Gene Editing in HIV-1/AIDS Therapy

Frontiers in Cellular and Infection Microbiology, Год журнала: 2019, Номер 9

Опубликована: Март 22, 2019

Despite the fact that great efforts have been made in prevention and resistance of HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. Highly active antiretroviral therapy (HAART) can suppress virus replication, but it cannot eradicate latent viral reservoirs patients. Recently, clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system has engineered as an effective gene-editing technology with potential treat HIV-1/AIDS. It be used target cellular co-factors or genome reduce infection clear provirus, well induce transcriptional activation for elimination. This versatile gene editing successfully applied reduction cells animal models. Here, we update rapid progress CRISPR/Cas9-based research recent years discuss limitations future perspectives its application.

Язык: Английский

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Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview

Vaccines, Год журнала: 2025, Номер 13(2), С. 148 - 148

Опубликована: Янв. 31, 2025

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements our understanding HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines mRNA technology induce broadly neutralizing antibodies, have shown promise. However, efficacy these modest, with best results achieving approximately 30% effectiveness. Ongoing research emphasizes necessity multifaceted strategy overcome obstacles achieve breakthrough development. This review summarizes current approaches utilized further understand create global vaccine. We discuss impact on for other diseases, COVID-19, influenza, Zika virus. Additionally, we highlight specific limitations faced each approach present methods researchers employ challenges. These techniques, which demonstrated preclinical clinical success, advanced field closer ultimate goal developing Leveraging will enable strides combating infectious ultimately improving health outcomes.

Язык: Английский

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Barriers for HIV Cure: The Latent Reservoir

AIDS Research and Human Retroviruses, Год журнала: 2018, Номер 34(9), С. 739 - 759

Опубликована: Июль 28, 2018

Thirty-five years after the identification of HIV-1 as causative agent AIDS, we are still in search vaccines and treatments to eradicate this devastating infectious disease. Progress has been made understanding molecular pathogenesis infection, which crucial for development current therapy regimens. However, despite their efficacy at limiting active viral replication, these drugs unable purge latent reservoir: a pool cells that harbor transcriptionally inactive, but replication-competent proviruses, represent main barrier from affected individuals. In review, discuss advances field have allowed better latency, including diverse cell types constitute reservoir, factors influencing tools study well prospective therapeutic approaches target latently infected cells, so functional cure HIV/AIDS can become reality.

Язык: Английский

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Efficient inhibition of African swine fever virus replication by CRISPR/Cas9 targeting of the viral p30 gene (CP204L)

Scientific Reports, Год журнала: 2018, Номер 8(1)

Опубликована: Янв. 17, 2018

Abstract African swine fever is a devastating viral disease of domestic and wild pigs against which no vaccine or therapy available. Therefore, we applied the CRISPR (clustered regularly interspaced short palindromic repeats) – Cas9 nuclease system to target double-stranded DNA genome virus (ASFV). To this end, permissive boar lung (WSL) cell line was modified by stable transfection with plasmid encoding guide RNA targeting codons 71 78 phosphoprotein p30 gene (CP204L) ASFV. Due targeted cleavage genome, plaque formation ASFV completely abrogated yields were reduced four orders magnitude. The specificity these effects could be demonstrated using natural isolate escape mutants possessing nucleotide exchanges within sequence, not inhibited in Cas9-expressing line. Growth affected transgene expression which, as well inhibition, proved over at least 50 passages. Thus, CRISPR-Cas9 mediated valid strategy convey resistance ASF infection, may also its animal host.

Язык: Английский

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Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease

Molecular Therapy — Methods & Clinical Development, Год журнала: 2020, Номер 18, С. 532 - 557

Опубликована: Июль 4, 2020

We present an overview of clinical trials involving gene editing using clustered interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), or zinc finger (ZFNs) and discuss the underlying mechanisms. In cancer immunotherapy, is applied ex vivo in T cells, transgenic cell receptor (tTCR)-T chimeric antigen (CAR)-T cells to improve adoptive therapy for multiple types. This involves knockouts immune checkpoint regulators such as PD-1, components endogenous TCR histocompatibility leukocyte (HLA) complex generate universal allogeneic CAR-T CD7 prevent self-destruction therapy. cervix carcinoma caused by human papillomavirus (HPV), E6 E7 genes are disrupted topically machinery. HIV infection, CCR5 co-receptor HIV-resistant hematopoietic stem cells. β-thalassemia sickle disease, engineered induce production fetal hemoglobin. AAV-mediated exploit liver systemic therapeutic proteins hemophilia mucopolysaccharidoses, eye restore splicing CEP920 Leber's congenital amaurosis. Close consideration safety aspects education stakeholders will be essential a successful implementation technology clinic.

Язык: Английский

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Characterization of HIV-1 Infection in Microglia-Containing Human Cerebral Organoids

Viruses, Год журнала: 2022, Номер 14(4), С. 829 - 829

Опубликована: Апрель 16, 2022

The achievement of an HIV cure is dependent on the eradication or permanent silencing HIV-latent viral reservoirs, including understudied central nervous system (CNS) reservoir. This requires a deep understanding molecular mechanisms HIV's entry into CNS, latency establishment, persistence, and reversal. Therefore, representative CNS culture models that reflect intercellular dynamics pathophysiology human brain are urgently needed in order to study reservoir HIV-induced neuropathogenesis. In this study, we characterized cerebral organoid model which microglia grow intrinsically as infection CNS. We demonstrated both organoids isolated organoid-derived (oMG), infected with replication-competent HIVbal reporter viruses, support productive via CCR5 co-receptor. Productive was only observed microglial cells. Fluorescence analysis revealed target cell. Susceptibility co-expression microglia-specific markers CD4 receptors. Altogether, will be valuable tool within research community HIV-CNS interactions, underlying HIV-associated neurological disorders (HAND), efficacy new therapeutic curative strategies

Язык: Английский

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CRISPR/Cas9: a tool to eradicate HIV-1

AIDS Research and Therapy, Год журнала: 2022, Номер 19(1)

Опубликована: Дек. 1, 2022

Abstract The development of antiretroviral therapy (ART) has been effective in suppressing HIV replication. However, severe drug toxicities due to the and its failure targeting integrated proviral genome have led introduction a new paradigm gene-based therapies. With inhibition high precision, clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) or CRISPR/Cas9 emerged as an editing tool last decade. Mediated by guide RNAs (gRNAs), Cas9 endonuclease acts like genetic scissors that can modify specific target sites. this concept, used HIV-1 both vitro well vivo studies including non-human primates. CRISPR also tested for latent modulating transcription with help specialized mutant. Overcoming limitations current therapy, potential become primary eradicating infection. In review, we summarize recent advancements genome, challenges future prospects.

Язык: Английский

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Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 148, С. 112743 - 112743

Опубликована: Фев. 25, 2022

Viral infections are a common cause of morbidity worldwide. The emergence Coronavirus Disease 2019 (COVID-19) has led to more attention viral and finding novel therapeutics. CRISPR-Cas9 system been recently proposed as potential therapeutic tool for the treatment diseases. Here, we review research progress in use CRISPR-Cas technology treating infections, well strategies improving delivery this gene-editing vivo. Key challenges that hinder widespread clinical application also discussed, several possible directions future proposed.

Язык: Английский

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Harnessing CRISPR technology for viral therapeutics and vaccines: from preclinical studies to clinical applications

Virus Research, Год журнала: 2024, Номер 341, С. 199314 - 199314

Опубликована: Янв. 13, 2024

The CRISPR/Cas system, identified as a type of bacterial adaptive immune have attracted significant attention due to its remarkable ability precisely detect and eliminate foreign genetic material nucleic acids. Expanding upon these inherent capabilities, recent investigations unveiled the potential reprogrammed 9, 12, 13 systems for treating viral infections associated with human diseases, specifically targeting DNA RNA viruses, respectively. Of particular interest is virus responsible global outbreak coronavirus disease 2019 (COVID-19), which presents substantial public health risk, coupled limited efficacy current prophylactic therapeutic techniques. In this regard, utilization technology offers promising gene editing approach overcome limitations conventional methods in managing infections. This comprehensive review provides an overview latest CRISPR/Cas-based vaccine strategies employed combat Additionally, we discuss challenges offer insights into future prospects cutting-edge technology.

Язык: Английский

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Breaking Barriers to an HIV-1 Cure: Innovations in Gene Editing, Immune Modulation, and Reservoir Eradication

Life, Год журнала: 2025, Номер 15(2), С. 276 - 276

Опубликована: Фев. 11, 2025

Recent advances in virology, particularly the study of HIV-1, have significantly progressed pursuit a definitive cure for disease. Emerging therapeutic strategies encompass innovative gene-editing technologies, immune-modulatory interventions, and next-generation antiretroviral agents. Efforts to eliminate or control viral reservoirs also gained momentum, with aim achieving durable remission without continuous requirement therapy. Despite these promising developments, critical challenges persist bridging gap between laboratory findings clinical implementation. This review provides comprehensive analysis recent breakthroughs, ongoing trials, barriers that must be addressed translate advancements into effective treatments, emphasizing multifaceted approaches being pursued achieve curative solution HIV-1 infection.

Язык: Английский

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