XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection

Article Medicine, Research & Experimental

A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant

Yi-Chung Chang et al.

Summary: The inhalable siRNA drug C6G25S, covering 99.8% of SARS-CoV-2 variants, shows effectiveness in inhibiting dominant strains and preventing lung damage in animal models.

EMBO MOLECULAR MEDICINE (2022)

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Article Chemistry, Multidisciplinary

Aptamers Entirely Built from Therapeutic Nucleoside Analogues for Targeted Cancer Therapy

Lijuan Zhu et al.

Summary: Aptamer-drug conjugates (ApDCs) are a promising drug delivery system for targeted cancer therapy. However, the conventional ApDC has limited drug loading capacity. To address this challenge, researchers have developed drugtamers, whole drug-constituted DNA-like oligomers, which have 100% drug loading ratio, active targeting capability, and enzyme-mediated release of active therapeutics.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022)

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Article Multidisciplinary Sciences

Considerable escape of SARS-CoV-2 Omicron to antibody neutralization

Delphine Planas et al.

Summary: The Omicron variant of SARS-CoV-2, identified in November 2021, has spread rapidly worldwide and shows resistance to most therapeutic monoclonal antibodies and vaccine-elicited antibodies. However, it can be neutralized by antibodies generated by a booster vaccine dose.

NATURE (2022)

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Article Biochemistry & Molecular Biology

Bind, cleave and leave: multiple turnover catalysis of RNA cleavage by bulge-loop inducing supramolecular conjugates

Bahareh Amirloo et al.

Summary: The use of catalytic peptides in antisense oligonucleotides allows for turnover of targeted RNA, facilitating cleavage and release of catalyst for further attacks on RNA substrates. This approach shows promise for achieving knockdown of RNA copy numbers with limited catalytic molecules, and further research is needed to accelerate the destruction of different RNA targets.

NUCLEIC ACIDS RESEARCH (2022)

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Article Biochemistry & Molecular Biology

Targeting genomic SARS-CoV-2 RNA with siRNAs allows efficient inhibition of viral replication and spread

Shubhankar Ambike et al.

Summary: Small interfering (si)RNAs could be a promising approach to tackle SARS-CoV-2. Research shows that siRNAs can target the genomic RNA (gRNA) of the virus after cell entry, thereby terminating replication before transcription starts and preventing virus-induced cell death. Targeting common sequences shared by viral transcripts allows simultaneous suppression of gRNA and subgenomic (sg)RNAs, while specifically targeting the gRNA, especially open reading frame 1(ORF1), leads to the most effective suppression of viral replication and spread.

NUCLEIC ACIDS RESEARCH (2022)

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Article Microbiology

A protease-activatable luminescent biosensor and reporter cell line for authentic SARS-CoV-2 infection

Pehuen Pereyra Gerber et al.

Summary: In this study, a new method for measuring SARS-CoV-2 infection is described which is simpler and faster than existing methods. It relies on the reaction between a specific protease enzyme produced by the virus and an engineered protein biosensor to detect infection. This method can be used to detect different variants of SARS-CoV-2 and quantify neutralising antibodies.

PLOS PATHOGENS (2022)

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Article Biology

Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences

Jeffrey Y. Lee et al.

Summary: Despite extensive research, early replication events of SARS-CoV-2 are still poorly understood. This study used smFISH to quantify viral RNA and found that SARS-CoV-2 genomic RNA has a long lifespan in cells and replication varies significantly between cells. Additionally, the B.1.1.7 variant exhibits slower replication kinetics than the Victoria strain, suggesting a novel mechanism contributing to its higher transmissibility.

ELIFE (2022)

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Review Biochemical Research Methods

New chemistries and enzymes for synthetic genetics

Niklas Freund et al.

Summary: Nucleic acid chemistry has led to modifications of DNA and RNA structures, creating xeno-nucleic acids (XNAs) that are not naturally found and can be used in synthetic genetics for encoded synthesis, reverse transcription, and evolution.

CURRENT OPINION IN BIOTECHNOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Selection and Validation of siRNAs Preventing Uptake and Replication of SARS-CoV-2

Maik Friedrich et al.

Summary: In 2019, the SARS-CoV-2 outbreak caused a global pandemic. Besides vaccines, there is a need for novel treatment options. The use of siRNA targeting ACE2 and the SARS-CoV-2 RNA genome is an effective strategy to prevent viral entry into host cells or interfere with viral replication.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2022)

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Article Chemistry, Multidisciplinary

A modular XNAzyme cleaves long, structured RNAs under physiological conditions and enables allele-specific gene silencing

Alexander Taylor et al.

Summary: This study reports the development of a highly specific RNA endonuclease XNAzyme, FR6_1, that can cleave highly structured full-length mRNA with allelic selectivity for tumor-associated mutations. This research provides a starting point for the development of improved gene-silencing agents based on FANA or other XNA chemistries.

NATURE CHEMISTRY (2022)

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Review Microbiology

Characteristics of SARS-CoV-2 and COVID-19

Ben Hu et al.

Summary: This review summarizes the research progress on SARS-CoV-2 and COVID-19, including virology characteristics, pathogenesis, and recent advances in treatment methods. Furthermore, it discusses in detail the potential wildlife hosts and zoonotic origin of this emerging virus.

NATURE REVIEWS MICROBIOLOGY (2021)

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Editorial Material Medicine, General & Internal

A Large, Simple Trial Leading to Complex Questions

David P. Harrington et al.

Summary: The study reported preliminary results of several pharmacologic treatments that have generated substantial interest in clinical trials, involving 405 hospitals in 30 countries worldwide. These treatments are based on remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Immunology

SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

Nikolaos C. Kyriakidis et al.

Summary: The new SARS-CoV-2 virus is rapidly spreading worldwide, causing the COVID-19 pandemic with more than 1.866 million deaths. Over 64 vaccine candidates are being developed globally, aiming to induce antibodies to prevent viral entry. Thirteen vaccine candidates are currently in Phase 3 clinical trials, showing promising progress towards approval for large-scale immunizations.

NPJ VACCINES (2021)

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Article Biochemistry & Molecular Biology

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Elettra Barberis et al.

Summary: Limited knowledge of the host response to SARS-CoV-2 hinders understanding of COVID-19 pathogenesis and therapeutic strategies. This study revealed that SARS-CoV-2 infection modulates exosome content and their involvement in disease progression, highlighting the potential of plasma exosomes as biomarkers for disease severity. Proteomic analysis of patient-derived exosomes identified molecules implicated in immune response, inflammation, coagulation, and complement pathways associated with COVID-19 tissue damage and organ dysfunction. Moreover, the presence of SARS-CoV-2 RNA in exosomes suggests a potential route for viral spread.

FRONTIERS IN MOLECULAR BIOSCIENCES (2021)

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Review Microbiology

Nucleic Acid-Based Treatments Against COVID-19: Potential Efficacy of Aptamers and siRNAs

Javad Khanali et al.

Summary: Despite the lack of approved treatments for COVID-19, biotechnological approaches such as aptamers and siRNAs show promise. These nucleic acid-based therapies have the potential to hinder viral entry, replication, and reduce viral loads, suggesting their application in combating SARS-CoV-2.

FRONTIERS IN MICROBIOLOGY (2021)

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Review Chemistry, Multidisciplinary

Inhibition of SARS-CoV-2 by Targeting Conserved Viral RNA Structures and Sequences

Shalakha Hegde et al.

Summary: The ongoing COVID-19 pandemic has had a significant impact on global public health and society, with research on targeting conserved SARS-CoV-2 RNA structures and sequences emerging as a promising new approach to inhibit viral infection. These RNA-targeting molecules could serve as an emerging class of antiviral drug candidates for future viral outbreaks.

FRONTIERS IN CHEMISTRY (2021)

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Article Virology

Targeting the Conserved Stem Loop 2 Motif in the SARS-CoV-2 Genome

Valeria Lulla et al.

Summary: The highly conserved s2m element found in many RNA viruses, including SARS-CoV-2, can be targeted by ASOs, showing potential as antiviral agents for further research.

JOURNAL OF VIROLOGY (2021)

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Review Medicine, Research & Experimental

siRNA Therapeutics for the Therapy of COVID-19 and Other Coronaviruses

Muhammad Imran Sajid et al.

Summary: The ongoing global pandemic has caused millions of deaths and affected around 151 million people worldwide. Despite the hope brought by vaccines for COVID-19, researchers are still seeking new ways to combat the viral pandemic. RNA interference (RNAi) has emerged as a promising antiviral agent, with the potential for significant impact in treating coronaviruses.

MOLECULAR PHARMACEUTICS (2021)

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Article Biotechnology & Applied Microbiology

A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19

Adi Idris et al.

Summary: This study presents a highly effective siRNA therapeutic against SARS-CoV-2 infection using a novel LNP delivery system, with the potential to significantly inhibit the virus in the lungs and provide a survival advantage to treated mice.

MOLECULAR THERAPY (2021)

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Article Chemistry, Multidisciplinary

A biologically stable DNAzyme that efficiently silences gene expression in cells

Yajun Wang et al.

Summary: Efforts to use RNA-cleaving DNA enzymes as gene-silencing agents have been hindered by low efficacy in clinical trials, but a new xeno-nucleic-acid-modified DNAzyme called X10-23 has shown promise in achieving multiple-turnover activity and resisting nuclease digestion in cellular conditions. X10-23 overcomes product inhibition and facilitates persistent gene silencing in mammalian cells, suggesting new molecular chemotypes can enhance the activity and stability of DNAzymes for potential therapeutic applications.

NATURE CHEMISTRY (2021)

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Article Multidisciplinary Sciences

The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA

Jasmine Cubuk et al.

Summary: The study reveals that SARS-CoV-2 nucleocapsid (N) protein undergoes liquid-liquid phase separation with RNA, and provides molecular details of N protein through single-molecule spectroscopy with all-atom simulations, showing its multivalent RNA-binding nature and interactions that may drive RNA compaction.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

A small interfering RNA (siRNA) database for SARS-CoV-2

Inacio Gomes Medeiros et al.

Summary: This work presents a database of SARS-CoV-2 targets for small interference RNA (siRNA) based approaches, aiming to expedite the design process of antivirals. The siRNA sequences are characterized and evaluated by over 170 features, providing diversity for technology and expertise in laboratories worldwide.

SCIENTIFIC REPORTS (2021)

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Article Chemistry, Multidisciplinary

REVEALR: A Multicomponent XNAzyme-Based Nucleic Acid Detection System for SARS-CoV-2

Kefan Yang et al.

Summary: The study introduces a highly sensitive multicomponent XNA-based nucleic acid detection platform, termed REVEALR, with a detection limit of <= 20 aM and a total assay time of 1 h for detecting the viral pathogen responsible for COVID-19. This platform offers a convenient nucleic acid alternative to equivalent CRISPR-based approaches and shows perfect accuracy against COVID-19 patient-derived clinical samples with no cross-reactivity to other in vitro transcribed respiratory viral RNAs.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Review Nanoscience & Nanotechnology

The current landscape of nucleic acid therapeutics

Jayesh A. Kulkarni et al.

Summary: The increasing number of approved nucleic acid therapeutics demonstrates their potential for long-lasting or curative effects by targeting genetic blueprints; however, their clinical translation relies on advances in delivery technologies. Four platform technologies, including antisense oligonucleotides, small interfering RNA conjugates, lipid nanoparticles, and adeno-associated virus vectors, have enabled the clinical translation of nucleic acid therapeutics, leading to the approval of cutting-edge genetic drugs.

NATURE NANOTECHNOLOGY (2021)

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Review Microbiology

SARS-CoV-2 variants, spike mutations and immune escape

William T. Harvey et al.

Summary: The evolution of SARS-CoV-2 has been characterized by the emergence of mutations and variants that impact virus characteristics. Manufacturers are preparing for possible updates to vaccines in response to changes in the virus population, and it is crucial to monitor genetic and antigenic changes alongside experiments to understand the impacts of mutations.

NATURE REVIEWS MICROBIOLOGY (2021)

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Article Multidisciplinary Sciences

The architecture of the SARS-CoV-2 RNA genome inside virion

Changchang Cao et al.

Summary: Researchers have used vRIC-seq technology to reveal the tertiary structure of the SARS-CoV-2 genome in virions, finding an unentangled globule conformation. They also discovered the role of long-range duplexes and higher-order junctions in the sequential packaging of the viral genome, with some mutations potentially contributing to more stable duplex structures.

NATURE COMMUNICATIONS (2021)

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Article Biotechnology & Applied Microbiology

The Application of CRISPR/Cas Systems for Antiviral Therapy

Helen J. E. Baddeley et al.

Summary: As CRISPR/Cas systems have evolved, efforts have been made to use them in developing sequence-targeted antiviral therapies. Various CRISPR systems can directly cleave viral genomes, providing potential for preventing or treating infections. Recent studies have shown promising results using different Cas effectors against various types of viruses, with remaining challenges in tackling newly emerging viruses.

FRONTIERS IN GENOME EDITING (2021)

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Article Biochemistry & Molecular Biology

Developing effective siRNAs to reduce the expression of key viral genes of COVID-19

Renfei Wu et al.

Summary: This study proposes the application of siRNAs to degrade the viral genome for reducing COVID-19 infection, and designs 11 siRNAs targeting consensus regions of SARS-CoV-2, showing that most siRNAs could significantly reduce viral gene expression.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2021)

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Coronavirus biology and replication: implications for SARS-CoV-2

Philip V'kovski et al.

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Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza

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XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection

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