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Biochemistry, Genetics and Molecular Biology · Research topic

Open research questions in Virus-based gene therapy research

34 unresolved questions extracted from the limitations and future-work sections of 220 Virus-based gene therapy research papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Orthoflaviviruses depend on host metabolic resources to replicate, but how distinct cell types in the central nervous system (CNS) alter their metabolism in response to infection remains incompletely understood.

    SIRT1 remodels astrocyte metabolism and promotes viral replication during neurotropic orthoflavivirus infection · 2026 · DOI

  • Moreover, the globally distributed MaAv lymphocytic chori-omeningitis virus (LCMV) is an underrecognized pathogen of clinical significance in congenital infections and immunocompromised individuals.

    Sirtuin 1 Is Required for Optimal Mammarenavirus Multiplication · 2026 · DOI

  • Severe acute respiratory syndrome coronavirus 2 assembles at the ER Golgi intermediate compartment (ERGIC), yet the molecular basis of nucleocapsid (N) protein interactions with host membranes remains unclear.

    SARS-CoV-2 nucleocapsid protein engages with viral RNA and ERGIC lipids to drive viral core assembly · 2026 · DOI

  • Although several ERV-derived proteins promote membrane fusion, little is known about evolutionarily conserved mechanisms that negatively regulate this process.

    Mouse suppressyn-like 1 is an endogenous retrovirus-derived inhibitor of membrane fusion through direct association with envelope glycoproteins · 2026 · DOI

  • Extracellular matrix (ECM) regulates tumor architecture and immune accessibility, but its impact on virus-based anticancer therapies is not well understood.

    Distinct Effects of the Extracellular Matrix on Tumor Organization and Response to Cancer Virotherapy · 2026 · DOI

  • It can be concluded that if this noninvasive route has to be chosen, a much higher dose is warranted, which will exacerbate systemic toxic- ity. Therefore, to support the notion that the IST route is optimal, further studies are warranted to determine if the improved pharmacodynamic benefits outweigh side effects related to this surgical procedure [33].

    QSP model for AAV-mediated antibody delivery in rat brain · 2026 · DOI

  • ABSTRACT Coronavirus particles assemble at endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membranes and exit from host cells via secretory organelles that are not well defined.

    Coronavirus membrane protein with a fluorescent protein tag enables particle tracking for the study of virus assembly and egress in live cells · 2026 · DOI

  • The role of NSm during replication in mammalian cells is poorly characterized, although it associates with a Golgi-derived structure called the virus factory (VF), the site of BUNV genome replication and virion assembly.

    Interaction of Bunyamwera Virus Non-Structural Protein NSm with Cellular BNIP1 is Required for Efficient Viral Gene Expression and Replication · 2026 · DOI

  • Although various AAVs have been identified for their ability to transduce different cells in the CNS, their effectiveness and efficiency are significantly limited by the presence of neutralising antibodies (NAbs) and restricted cargo capacity.

    Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS) · 2026 · DOI

  • The loss of Neu4,5Ac2 preceded the reduction in ISAV-bound erythrocytes by several days, indicating that receptor removal alone was insufficient to trigger virion release.

    Common ISAV haemagglutinin esterase variants at residues 229 and 230 influence the efficiency of receptor destruction and erythrocyte release in Atlantic salmon · 2026 · DOI

  • The ISAV esterase removes the virus-targeted epitope and causes homologous attachment interference, but its broader biological roles remain poorly understood.

    Common ISAV haemagglutinin esterase variants at residues 229 and 230 influence the efficiency of receptor destruction and erythrocyte release in Atlantic salmon · 2026 · DOI

  • Furthermore, differential incorporation of IFITMs into HIV-1 virions did not consistently correlate with antiviral activity, indicating that virion incorporation alone is insufficient to explain HIV-1 restriction.

    Gene duplication and retrotransposition diversify the antiviral repertoire of macaque IFITM proteins · 2026 · DOI

  • SignificanceRecombinant adeno-associated viruses (rAAVs) are widely used gene delivery vectors, yet the intracellular trafficking steps that enable productive transduction remain incompletely defined.

    TBC1D23-AAVR Interaction Drives Endosome-to-TGN Trafficking Required for rAAV Transduction · 2026 · DOI

  • While chemical cell lysis that releases MVA particles into the supernatant before clarification can greatly enhance process efficiency and scalability, this step remains insufficiently characterized.

    Chemical Cell Lysis with Clarification Filtration of Suspension Cell Culture-Derived Modified Vaccinia Virus Ankara · 2026 · DOI

  • Although antibody-armed OVs have demonstrated significant therapeutic potential, their clinical application remains in the early phases (Table 1). Several barriers hinder their broad translation. Safety and tolerability require careful optimization, as OVs may trigger systemic inflammatory responses (52). In vivo viral spread is often restricted by host neutralizing antibodies, tissue barriers, and limiting delivery efficiency (53). extracellular matrices, Furthermore, clinical quality control for these complex, dual- action biologicals requires more rigorous potency assays than conventional monoclonal antibodies. Future directions must focus on optimizing viral shielding (e.g., nanoparticle coatings to evade neutralizing antibodies for IV delivery), refining synthetic promoters to restrict antibody expression strictly to the tumor site, and exploring rational combinations with adoptive cell therapies (like CAR-T) to fully leverage the inflamed TME (54, 55).

    Engineering antibody-armed oncolytic viruses: design strategies, synergistic mechanisms, and clinical translation · 2026 · DOI

  • However, a number of issues remain to be resolved, such as variable treatment effects, anti-AAV capsid-neutraliz- ing antibodies, and its indication for children.

    Gene Therapy: Current status and Future Perspective · 2026 · DOI

  • A number of issues remain to be resolved, such as variable treatment effects, anti-AAV capsid-neutralizing antibodies, and its indication for children.

    Gene Therapy: Current status and Future Perspective · 2026 · DOI

  • Yet, host pathways that sense TONV infection and restrict its replication remain poorly defined.

    The RLR-MAVS-IRF3 axis activates the IFN pathway to restrict Tonate virus (TONV) infection · 2026 · DOI

  • The interplay between viral components and intracellular transport pathways that facilitate assembly and egress is not fully understood, and recent studies suggest that multiple pathways may be involved.

    Coronavirus membrane protein with a fluorescent protein tag enables particle tracking for the study of virus assembly and egress in live cells · 2026 · DOI

  • The direction of gene of interest (GOI) cannot be ensured when linear DNA is inserted at the NHEJ site.

    Gene Therapy: Current status and Future Perspective · 2026 · DOI

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34 open questions have been extracted from the limitations and future-work passages of 220 Virus-based gene therapy research papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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