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Biochemistry, Genetics and Molecular Biology · Research topic

Open research questions in Virus-based gene therapy research

703 gap statements mined from Virus-based gene therapy research papers in our 7.9M-paper local library, which holds 2,668 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • While radiolabelled autologous leukocytes and 18F-FDG remain valuable diagnostic tools, their inherent limitations in pathogen specificity often leave clinicians without a clear microbiological answer, leading to suboptimal or delayed targeted therapies.

    Nuclear medicine for the diagnosis of infectious diseases: can we improve? · 2026 · DOI

  • A major strength of this study is the combined use of clinical observations, molecular characterization, phylogenetic analysis, and viral pathogenicity, which together confirm the circulating of FAdV-2/11 strains in a region that remains poorly investigated.

    Pathogenicity and Genotyping of Fowl Adenovirus-D Serotype 2/11 Circulating in Commercial Broilers in Egypt · 2026 · DOI

  • Oncolytic viruses represent a transformative approach to cancer immunotherapy that addresses the fundamental limitation of immune checkpoint inhibitors: the inability to generate de novo immune responses in immunologically cold tumors lacking pre-existing T cell infiltration.

    Oncolytic Virotherapy and Immunogenic Cell Death: Mechanisms, Platforms, and Clinical Translation · 2026 · DOI

  • Catumaxomab, supported by randomized phase III evidence, has demonstrated consistent benefit in prolonging puncture-free survival, though its overall survival effect is limited to the gastric cancer subgroup and the drug has undergone regulatory withdrawal and reauthorization.

    Emerging innovative immunotherapies in malignant ascites: current landscape, challenges and perspectives · 2026 · DOI

  • Current evidence supports feasibility and pharmacodynamic activity for selected platforms and defines a negative clinical boundary the incremental efficacy of OV-containing regimens remains to be established in contemporary comparator-controlled studies.

    Liver-resident cellular determinants of oncolytic virotherapy in hepatocellular carcinoma: viral susceptibility and spatial immune remodeling · 2026 · DOI

  • Evidence that local infection reproducibly remodels non-injected disease or that adding an OV improves a contemporary ICI or locoregional backbone remains insufficient.

    Liver-resident cellular determinants of oncolytic virotherapy in hepatocellular carcinoma: viral susceptibility and spatial immune remodeling · 2026 · DOI

  • While we did not explore SHIV neutralizing antibody responses in this study, further investigation of the impact of IgG-cleaving enzymes on the functionality of the Env-specific humoral response is warranted, particularly as recent studies have highlighted the role of autologous neutralizing antibodies in post-treatment HIV control.

    IgM-and IgG-cleaving enzyme facilitates AAV gene transfer in AAV-seropositive macaques · 2026 · DOI

  • The limited flexibility of the Mono-Bac system. The lack of rapid quantification of infectious rBV titers.

    A mMono-Bac1.0 system for recombinant adeno-associated virus vectors with higher flexibility, throughput and yield · 2026 · DOI

  • The high manufacturing cost remains a major barrier to broader clinical translation. The lack of rapid and accurate method for monitoring rBV concentrations in culture supernatants remains a major limitation. The Mono-Bac system has limited flexibility due to its architecture. The construction of the pFD/Cap-(ITR-GOI)-Rep transfer vector is technically challenging.

    A mMono-Bac1.0 system for recombinant adeno-associated virus vectors with higher flexibility, throughput and yield · 2026 · DOI

  • Newcastle disease virus (NDV) is an oncolytic virus with selective antitumor activity, but the molecular mechanisms by which NDV disrupts oncogenic signaling remain incompletely understood.

    Oncolytic Newcastle disease virus promotes tumor cell apoptosis through SUMO-1-dependent PRKN-mediated degradation of c-Myc · 2026 · DOI

  • Although transmission between domestic and wild carnivores has been reported, the direction of this spillover and the role of wildlife in long-term virus persistence are still not well understood.

    Red Foxes (Vulpes vulpes) and European Badgers (Meles meles) as Overlooked Wildlife Hosts of Canine Parvovirus in Slovakia: First Evidence by Molecular Characterization and Virus Isolation · 2025 · DOI

  • The role of OVs in the neoadjuvant setting remains unclear in the era of preoperative anti-PD-1 therapy. Additional clinical scenarios that could benefit from OVs are envisioned but remain to be explored.

    The Evolution, Current Landscape, and Future Prospects of Oncolytic Virotherapy in Melanoma: Talimogene Laherparepvec and Beyond · 2025 · DOI

  • While this is currently promising, monoclonal antibodies beyond ICIs, such as those targeting EGFR or VEGF, are comparatively understudied in combination with OVs. These advancements highlight the validated clinical potential for viroimmunotherapy, but CRC-specific efficacy data remain sparse.

    Oncolytic Virotherapy in Colorectal Cancer: Mechanistic Insights, Enhancer Strategies, and Translational Combinations · 2025 · DOI

  • A notable property of these particles is their capacity for replication, which is limited to a single round. This significantly expands the number of research groups that can participate in such studies globally, as some regions and countries have limited access to BSL-3 and BSL-4 facilities. Consequently, the biology of new emerging viruses can be understood within a relatively short timeframe.

    Pseudotyped Viruses: A Useful Platform for Pre-Clinical Studies Conducted in a BSL-2 Laboratory Setting · 2025 · DOI

  • The number of globally approved indications for OV products remains limited, and potential patient populations require further clinical research.

    Advances in the Drug Development and Quality Evaluation Principles of Oncolytic Herpes Simplex Virus · 2025 · DOI

  • Building on these encouraging findings, rSeVv-based vaccines warrant further exploration for the development of broad-spectrum vaccines targeting animal viruses. The strong innate immune activation triggered by rSeVv is particularly important for early viral control and supports their potential application in therapeutic settings, where they may contribute to reducing lesion severity and viral load.

    Recombinant Sendai Virus Vectors as Novel Vaccine Candidates Against Animal Viruses · 2025 · DOI

  • While the biological relevance of some capsid mutations remains unclear, sequencing and monitoring these changes in wild-host viruses is crucial.

    Molecular Survey for Major Canine Enteric Viral Pathogens in Wild Carnivores, Northwestern Italy · 2025 · DOI

  • Future research should address this limitation to further enhance the robustness and applicability of this diagnostic tool.

    Development of a Paper-Based Microfluidic Chip for Point-of-Care Detection of PEDV · 2025 · DOI

  • In light of the current vaccination recommendations, our findings suggest that improvements to all POCTs for detecting antibodies against CDV and CAV are warranted. Further evaluation of POCTs is warranted in healthy adult dogs at the time of scheduled triennial revaccination, as well as in subadult dogs following completion of puppy immunization.

    Antibody Titer Testing in Dogs: Evaluation of Three Point-of-Care Tests for Canine Core Vaccine Antigens Compared to Virus Neutralization · 2025 · DOI

  • Although fTfR1 may be similar to gpTfR1 in some respects, there are still differences between them, and further research is needed to verify the exact role of gpTfR1 in FPV infection. Future research is required to further explore the evolutionary path of FPV and its interaction with the host to comprehensively assess its potential impact on human health and implement corresponding prevention and control measures.

    The Giant Panda Transferrin Receptor Facilitates Feline Parvovirus Infection to Drive Cross-Species Transmission · 2025 · DOI

  • It has been reported that persistent post-entry barriers, such as reverse transcription, nuclear import, integration site selection, or chromatin-level regulation of transgene expression, likely remain operative and will require additional engineering to fully align murine T cells with their human counterparts, which is beyond the scope of this work.

    An inducible human LDLR transgenic mouse model for enhanced lentiviral gene delivery to murine immune cells · 2026 · DOI

  • Incorporation of synthetic biology elements (e.g., genetic logic gates, CRISPR-based targeting) may enhance selectivity. Armed constructs are expanding beyond cytokines to encode checkpoint inhibitors, stromal remodelers, or bispecific antibodies.

    Oncolytic Viruses in Glioblastoma: Clinical Progress, Mechanistic Insights, and Future Therapeutic Directions · 2025 · DOI

  • The BelloStage™-3000 system can be further explored for large-scale commercial vaccine production, demonstrating suitability for industrial applications, particularly in low- and middle-income countries where cost-effectiveness, reproducibility, and biosafety are essential.

    Efficient Serum-Free Rabies Virus Propagation Using BSR and Vero Cell Lines: A Comparative Evaluation of BioNOC II® Macrocarriers in the BelloStage™-3000 Bioreactor Versus Conventional Microcarriers · 2025 · DOI

  • Over the past decade, oncolytic virotherapy has rapidly progressed, with its primary goal shifting from merely causing direct tumor cell lysis to harnessing and enhancing virus-induced anti-tumor immune responses.

    A Comprehensive Review of Modern Cancer Therapies Utilizing Oncolytic Viruses · 2025 · DOI

  • This observation is consistent with findings from Denmark, where adenovirus F40/F41 was detected across various age groups, which suggests underrecognized adult infections.

    Genomic Epidemiological Characteristics of Enteric Adenovirus F40 and F41 in Yantai, China, from 2022 to 2023 · 2025 · DOI

Most-cited papers in Virus-based gene therapy research

Most recent work

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Open questions raised by papers listed on this page include: (1) The lack of rapid and accurate method for monitoring rBV concentrations in culture supernatants remains a major limitation (“A mMono-Bac1.0 system for recombinant adeno-associated virus vectors with…”, 2026); (2) Newcastle disease virus (NDV) is an oncolytic virus with selective antitumor activity, but the molecular mechanisms by which NDV disrupts oncogenic signaling remain incompletely understood (“Oncolytic Newcastle disease virus promotes tumor cell apoptosis through…”, 2026); (3) Although transmission between domestic and wild carnivores has been reported, the direction of this spillover and the role of wildlife in long-term virus persistence are still not well understood (“Red Foxes (Vulpes vulpes) and European Badgers (Meles meles) as Overlooked…”, 2025); (4) The role of OVs in the neoadjuvant setting remains unclear in the era of preoperative anti-PD-1 therapy (“The Evolution, Current Landscape, and Future Prospects of Oncolytic Virotherapy…”, 2025); (5) The number of globally approved indications for OV products remains limited, and potential patient populations require further clinical research (“Advances in the Drug Development and Quality Evaluation Principles of Oncolytic…”, 2025). 703 gap statements have been mined from Virus-based gene therapy research papers in our 7.9M-paper local library, which holds 2,668 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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