Viral vector platforms within the gene therapy landscape

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Feb. 8, 2021

Abstract Throughout its 40-year history, the field of gene therapy has been marked by many transitions. It seen great strides in combating human disease, given hope to patients and families with limited treatment options, but also subject setbacks. Treatment this class investigational drugs resulted severe adverse effects and, even rare cases, death. At heart dichotomous are viral-based vectors, delivery vehicles that have allowed researchers clinicians develop powerful drug platforms, radically changed face medicine. Within past 5 years, a wave based on viral vectors gained regulatory approval come variety designs purposes. These modalities range from vector-based cancer therapies, treating monogenic diseases life-altering outcomes. present, three key vector strategies adenoviruses, adeno-associated viruses, lentiviruses. They led way preclinical clinical successes two decades. However, despite these successes, challenges still limit approaches attaining their full potential. To review landscape, we focus highly regarded platforms describe mechanisms action roles disease.

Language: Английский

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Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: Dec. 6, 2018

Antiviral restriction factors are host cellular proteins that constitute a first line of defense blocking viral replication and propagation. In addition to interfering at critical steps the cycle, some also act as innate sensors triggering responses against infections. Accumulating evidence suggests an additional role for in promoting antiviral immunity combat viruses. Here, we review recent progress our understanding on how factors, particularly APOBEC3G, SAMHD1, Tetherin, TRIM5α have cell-autonomous potential induce resistance HIV-1 while adaptive immune responses. Also, provide overview these may connect with protein degradation pathways modulate anti-HIV-1 responses, summarize factors-based therapeutics. This brings global perspective influence restrictions intrinsic, innate, opening up novel research avenues therapeutic strategies fields drug discovery, gene therapy, vaccines control

Language: Английский

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Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens

Bioorganic & Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 46, P. 116356 - 116356

Published: Aug. 8, 2021

Language: Английский

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JAK-STAT Pathway: A Novel Target to Tackle Viral Infections

Viruses, Journal Year: 2021, Volume and Issue: 13(12), P. 2379 - 2379

Published: Nov. 27, 2021

Modulation of the antiviral innate immune response has been proposed as a putative cellular target for development novel pan-viral therapeutic strategies. The Janus kinase–signal transducer and activator transcription (JAK-STAT) pathway is especially relevant due to its essential role in regulation local systemic inflammation viral infections, being, therefore, target. Here, we review extraordinary diversity strategies that viruses have evolved interfere with JAK-STAT signaling, stressing relevance this Moreover, recent remarkable progress on JAK inhibitors (JAKi), current knowledge efficacy against distinct infections also discussed. JAKi proven broad spectrum disorders exhibit safety profiles comparable biologics, therefore representing good candidates drug repurposing strategies, including infections.

Language: Английский

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Highlighting membrane protein structure and function: A celebration of the Protein Data Bank

Journal of Biological Chemistry, Journal Year: 2021, Volume and Issue: 296, P. 100557 - 100557

Published: Jan. 1, 2021

Biological membranes define the boundaries of cells and compartmentalize chemical physical processes required for life. Many biological are carried out by proteins embedded in or associated with such membranes. Determination membrane protein (MP) structures at atomic near-atomic resolution plays a vital role elucidating their structural functional impact biology. This endeavor has determined 1198 unique MP as early 2021. The value these is expanded greatly deposition three-dimensional (3D) coordinates into Protein Data Bank (PDB) after first structure was elucidated 1985. Since then, free access to facilitates broader deeper understanding MPs, which provides crucial new insights functions. Here we highlight biology representative MPs landmarks evolution technologies, key developments influenced PDB magnifying impact.

Language: Английский

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Exploring precision treatments in immune‐mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery

Exploration, Journal Year: 2024, Volume and Issue: unknown

Published: May 24, 2024

Immune-mediated inflammatory diseases (IMIDs) impose an immeasurable burden on individuals and society. While the conventional use of immunosuppressants disease-modifying drugs has provided partial relief control, their inevitable side effects limited efficacy cast a shadow over finding cure. Promising nucleic acid have shown potential to exert precise at molecular level, with different classes acids having regulatory functions through varying mechanisms. For better delivery acids, safe effective viral vectors non-viral systems (including liposomes, polymers, etc.) been intensively explored. Herein, after describing range categories vectors, we focus application therapeutic in various IMIDs, including rheumatoid arthritis, bowel disease, psoriasis, multiple sclerosis, asthma, ankylosing spondylitis, systemic lupus erythematosus, uveitis. Molecules implicated inflammation immune dysregulation are abnormally expressed series meticulous modulation therapy results degrees remission improvement these diseases. By synthesizing findings centered specific targets, this review delivers systematic elucidation perspective towards advancing utilization therapeutics for managing IMIDs.

Language: Английский

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Sensor Sensibility—HIV-1 and the Innate Immune Response

Cells, Journal Year: 2020, Volume and Issue: 9(1), P. 254 - 254

Published: Jan. 20, 2020

Innate immunity represents the human immune system's first line of defense against a pathogenic intruder and is initiated by recognition conserved molecular structures known as pathogen-associated patterns (PAMPs) specialized cellular sensors, called pattern receptors (PRRs). Human immunodeficiency virus type 1 (HIV-1) unique RNA that causes acquired syndrome (AIDS) in infected individuals. During replication cycle, HIV-1 undergoes reverse transcription its genome integrates resulting DNA into genome. Subsequently, integrated provirus results production new virions spreading infection virus. Throughout viral numerous nucleic acid derived PAMPs can be recognized diverse set innate sensors cells. However, has evolved efficient strategies to evade or counteract this surveillance downstream responses. Understanding underpinnings concerted actions system, well corresponding evasion mechanisms during infection, critical understanding transmission pathogenesis, may provide important guidance for design appropriate adjuvant vaccine strategies. Here, we summarize current knowledge basis sensing cells, including CD4+ T dendritic macrophages. Furthermore, discuss underlying which regulated, describe developed

Language: Английский

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Multilayered and versatile inhibition of cellular antiviral factors by HIV and SIV accessory proteins

Cytokine & Growth Factor Reviews, Journal Year: 2018, Volume and Issue: 40, P. 3 - 12

Published: Feb. 23, 2018

Language: Английский

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Pleiotropic roles of the ubiquitin-proteasome system during viral propagation

Life Sciences, Journal Year: 2018, Volume and Issue: 207, P. 350 - 354

Published: June 18, 2018

Language: Английский

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The interaction of hepatitis B virus with the ubiquitin proteasome system in viral replication and associated pathogenesis

Virology Journal, Journal Year: 2019, Volume and Issue: 16(1)

Published: May 30, 2019

The ubiquitin proteasome system (UPS) regulates the expression levels of cellular proteins by ubiquitination protein substrates followed their degradation via proteasome. As a highly conserved mechanism, UPS affects variety biological processes and participates in viral propagation. During hepatitis B virus (HBV) infection, is shown to act as double-edged sword pathogenesis. On one hand, acts host defense mechanism selectively recognize HBV well special that favor life cycle induces ubiquitin-dependent proteasomal limit infection. other has evolved subvert function for its own advantage. Moreover, infected hepatocytes, certain are dependent on involved abnormal which mediated HBV. molecular interaction with modulate propagation pathogenesis summarized review. Considering important role better understanding HBV-UPS could provide novel insight into mechanisms replication help develop potential treatment strategies targeting UPS.

Language: Английский

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