Improved Cas9 activity by specific modifications of the tracrRNA DOI Creative Commons
Tristan Scott, Ryan Urak,

Citradewi Soemardy

et al.

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: Nov. 6, 2019

Abstract CRISPR/Cas is a transformative gene editing tool, that offers simple and effective way to target catalytic Cas9, the most widely used derived from Streptococcus pyogenes (Sp Cas9), with complementary small guide RNA (sgRNA) inactivate endogenous genes resulting insertions deletions (indels). CRISPR/Cas9 has been rapidly applied basic research as well expanded for potential clinical applications. Utilization of sp Cas9 an ribonuclearprotein complex (RNP) considered safe method apply technology, efficacy this system critically dependent on ability generate high levels indels. We find here novel sequence changes tracrRNA significantly improves activity when delivered RNP. demonstrate dual-guide (dgRNA) modified can improve reporter knockdown indel formation at several targets within long terminal repeat (LTR) HIV. Furthermore, sequence-modified tracrRNAs improved Cas9-mediated reduction CCR5 surface receptor expression in cell lines, which correlated higher formation. It was demonstrated RNP enhanced site primary CD4+ T-cells. Finally, we show two additional HBB locus BCL11A GATA site. Overall, data presented suggests facile could potentially be integrated current dgRNA open up possibility development activity.

Language: Английский

Microglial Cells: The Main HIV-1 Reservoir in the Brain DOI Creative Commons
Clémentine Wallet,

Marco De Rovere,

Jeanne Van Assche

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2019, Volume and Issue: 9

Published: Oct. 24, 2019

Despite efficient combination of the antiretroviral therapy (cART) which has significantly decreased mortality and morbidity HIV-1 infection, a definitive HIV cure not been achieved. Hidden in cellular anatomic reservoirs is major hurdle toward functional cure. Microglial cells, CNS resident macrophages, are one latent HIV-1. These cells believed to be involved both emergence drugs resistance reseeding peripheral tissues. Moreover, these long-life also development HIV-1-associated neurocognitive diseases (HAND). Clearing infected from brain therefore crucial achieve However, many characteristics microglial central nervous system might preclude eradication reservoirs. Better understandings specific molecular mechanisms latency should help design new molecules strategies preventing HAND achieving an needed circumvent limitations associated anatomical sanctuaries with barriers such as blood barrier (BBB) that reduce access drugs.

Language: Английский

Citations

316
Application of CRISPR/Cas9-Based Gene Editing in HIV-1/AIDS Therapy DOI Creative Commons
Qiaoqiao Xiao, Deyin Guo, Shuliang Chen

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2019, Volume and Issue: 9

Published: March 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.

Language: Английский

Citations

151
CRISPR-Cas Biology and Its Application to Infectious Diseases DOI Open Access
Jeffrey R. Strich, Daniel S. Chertow

Journal of Clinical Microbiology, Journal Year: 2019, Volume and Issue: 57(4)

Published: March 27, 2019

Infectious diseases remain a global threat contributing to excess morbidity and death annually, with the persistent potential for destabilizing pandemics. Improved understanding of pathogenesis bacteria, viruses, fungi, parasites, along rapid diagnosis treatment human infections, is essential improving infectious disease outcomes worldwide.

Language: Английский

Citations

135
Strategies to eradicate HIV from infected patients: elimination of latent provirus reservoirs DOI Creative Commons
Ivan Sadowski, Farhad B. Hashemi

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 76(18), P. 3583 - 3600

Published: May 25, 2019

35 years since identification of HIV as the causative agent AIDS, and million deaths associated with this disease, significant effort is now directed towards development potential cures. Current anti-retroviral (ART) therapies for HIV/AIDS can suppress virus replication to undetectable levels, infected individuals live symptom free so long treatment maintained. However, removal therapy allows rapid re-emergence from a highly stable reservoir latently cells that exist barrier elimination infection current ART. Prospects cure are significantly encouraged by two serendipitous cases where have entered remission following stem cell transplantation compatible HIV-resistant donors. routine could become available millions will require means specifically purging harboring latent HIV, preventing provirus, or destruction provirus genomes gene editing. Elimination exposing population, which may involve natural specific biomarker therapeutic intervention force their exposure reactivation expression. Accordingly, proposed "Shock Kill" strategy involves latency-reversing agents (LRA) induce expression thus these killing cellular immunity apoptosis. efforts enable at developing improved combinations LRA produce broad robust induction enhancing has been reactivated targeted immune modulation. Alternative strategies "Lock Block" intervention, transcription inhibited prevent spread disruption genome

Language: Английский

Citations

102
Barriers for HIV Cure: The Latent Reservoir DOI
Sergio Castro‐Gonzalez, Marta Colomer-Lluch, Ruth Serra-Moreno

et al.

AIDS Research and Human Retroviruses, Journal Year: 2018, Volume and Issue: 34(9), P. 739 - 759

Published: July 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.

Language: Английский

Citations

98
In Vivo T Cell-Targeting Nanoparticle Drug Delivery Systems: Considerations for Rational Design DOI
Paula M. Cevaal, Ali Abdalla, Ewa Czuba‐Wojnilowicz

et al.

ACS Nano, Journal Year: 2021, Volume and Issue: 15(3), P. 3736 - 3753

Published: Feb. 18, 2021

T cells play an important role in immunity and repair are implicated diseases, including blood cancers, viral infections, inflammation, making them attractive targets for the treatment prevention of diseases. Over recent years, advent nanomedicine has shown increase studies that use nanoparticles as carriers to deliver therapeutic cargo ex vivo applications. Nanoparticle-based delivery several advantages, ability load protect a variety drugs, control drug release, improve pharmacokinetics biodistribution, site- or cell-specific targeting. However, remains major technological challenge, which is primarily due nonphagocytic nature cells. In this review, we discuss physiological barriers effective cell targeting describe different approaches used cargo-loaded disease such lymphoma human immunodeficiency virus (HIV). particular, engineering strategies aim nanoparticle internalization by cells, ligand-based targeting, will be highlighted. These expected inspire development nanomaterials can target manipulate function cell-related

Language: Английский

Citations

71
Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections DOI Open Access
Sajad Najafi, Shing Cheng Tan, Shahin Aghamiri

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 148, P. 112743 - 112743

Published: Feb. 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.

Language: Английский

Citations

43
CRISPR/Cas9 Landscape: Current State and Future Perspectives DOI Open Access
Marina A. Tyumentseva, Marina A. Tyumentseva, В. Г. Акимкин

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16077 - 16077

Published: Nov. 8, 2023

CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 is a unique genome editing tool that can be easily used in wide range of applications, including functional genomics, transcriptomics, epigenetics, biotechnology, plant engineering, livestock breeding, gene therapy, diagnostics, and so on. This review focused on the current CRISPR/Cas9 landscape, e.g., Cas9 variants with improved properties, Cas9-derived fusion proteins, delivery methods, pre-existing immunity against anti-CRISPR their possible roles function improvement. Moreover, this presents detailed outline CRISPR/Cas9-based diagnostics therapeutic approaches. Finally, addresses future expansion editors’ toolbox orthologs other CRISPR/Cas proteins.

Language: Английский

Citations

32
Harnessing CRISPR technology for viral therapeutics and vaccines: from preclinical studies to clinical applications DOI Creative Commons

Farzaneh Zahedipour,

Fatemeh Zahedipour,

Parvin Zamani

et al.

Virus Research, Journal Year: 2024, Volume and Issue: 341, P. 199314 - 199314

Published: Jan. 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.

Language: Английский

Citations

9
Breaking Barriers to an HIV-1 Cure: Innovations in Gene Editing, Immune Modulation, and Reservoir Eradication DOI Creative Commons
Ana Borrajo

Life, Journal Year: 2025, Volume and Issue: 15(2), P. 276 - 276

Published: Feb. 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.

Language: Английский

Citations

1