Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody

Buchman, A.; Gamez, S.; Li, M.; Antoshechkin, I.; Lee, S.-H.; Wang, S.-W.; Chen, C.-H.; Klein, M. J.; Duchemin, J.-B.; Crowe, J. E.; Paradkar, P. N.; Akbari, O.

doi:10.1101/645481

bioRxiv · 10.1101/645481

Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody

Buchman, A.·Gamez, S.·Li, M.·Antoshechkin, I.·Lee, S.-H.·Wang, S.-W.·Chen, C.-H.·Klein, M. J.·Duchemin, J.-B.·Crowe, J. E.·Paradkar, P. N.·Akbari, O.

View original source ↗Export metadata ↓

Abstract

With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses.\n\nSignificance StatementHere we describe the development of Ae. aegypti mosquitoes synthetically engineered to impede vector competence to multiple serotypes of DENV. Given the global significance of DENV, these mosquitoes may be used to curtail Dengue transmission by this potent vector.

Source connections

Published article ↗

Explore related subjects

bioengineering Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Buchman, A., Gamez, S., Li, M., Antoshechkin, I., Lee, S.-H., Wang, S.-W., Chen, C.-H., Klein, M. J., Duchemin, J.-B., Crowe, J. E., Paradkar, P. N., Akbari, O.. 2019-05-24. Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody. https://doi.org/10.1101/645481

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Engineering and characterisation of AAVS1 FRT cell lines for inducible and dose-dependent gene expression

Investigating biological function with high reproducibility requires the generation of stable cell lines that offer precise and inducible transgene expression. However, traditional methods often suffer from the limitations of random genomic integration, including unpredictable expression levels, leaky basal activity, and disruption of endogenous loci. To address these challenges, we engineered a versatile RPE1 cell line by integrating a TetOn3G-FRT cassette into the AAVS1 safe-harbour locus using CRISPR/Cas9(D10A) nickase. This platform utilises the Flp-FRT recombination system to facilitate rapid, site-specific "plug-and-play" insertion of transgenes, combined with the Tet-On 3G system for tight, dose-dependent expression control. The resulting RPE1 AAVS1 FRT8 line enables highly consistent transgene induction across independent clones, behaving as a monoclonal population. We highlight the importance of rigorous cell line characterisation through a multi-omics approach. Whole genome sequencing identified precise heterozygous integration at the target locus and de novo genomic duplications on other chromosomes. By integrating WGS with high-resolution proteomics and cell cycle analysis, we confirmed that these alterations did not significantly perturb cellular homeostasis or phenotypic fitness. This work establishes a robust and reliable platform for the efficient generation of inducible AAVS1 FRT stable cell lines, facilitating reproducible research in modern molecular biology.

bioengineering↗

bioRxiv2026

Raman-probe-derived biomarkers account for cartilage composition, structure, and viscoelastic properties

Raman spectroscopy is an inelastic light scattering technique that reflects the vibrational modes of the biochemical building blocks of the major constituents that comprise the cartilage extracellular matrix (ECM): glycosaminoglycans (GAG), type-II collagen (COL), and water. We investigated whether ECM-specific biomarkers measured with our recently developed arthroscopy-compatible Raman needle probe characterize the functional viscoelastic properties of articular cartilage explants. Equine osteochondral explants were harvested from high-load (femoral condyle) and low-load (intertrochlear groove) sites to evaluate Raman-derived biomarkers of cartilage structure and function. Viscoelastic material properties (equilibrium/dynamic modulus, phase shift) were determined by mechanical indentation. A computational fibril-reinforced biphasic material model was used to estimate the glycosaminoglycan-associated non-fibrillar-matrix modulus, the collagen-associated fibril-network modulus, and hydraulic permeability. Raman-derived biomarkers enabled evaluation of cartilage tissue composition and structure, accounting for 81% of the variation in GAG content, 53% of the variation in COL content, and 58% of the variation in COL anisotropy. Biomarkers also accounted for 81% of the variation in equilibrium modulus, 58% in dynamic modulus, and 51% in phase shift. For poroelastic properties, biomarkers accounted for 83% of the variation in non-fibrillar-matrix modulus, 25% of the variation in fibril-network modulus, and 34% of the variation in hydraulic permeability. Clinical Significance: Raman spectroscopy provides objective compositional biomarkers that account for viscoelastic material properties underlying articular cartilage function. These findings support its future use as an arthroscopic platform for objective assessment of cartilage injury, monitoring of disease progression, and evaluation of therapeutic interventions.

bioengineering↗

bioRxiv2026

An adjuvant for in vivo CAR-T therapy potentiation against solid tumors

In vivo CAR-T therapy offers rapid and controllable T-cell engineering but has yet to achieve durable efficacy against solid tumors. Rather than focusing solely on CAR-T cells, we harness the intact immune system via an in vivo CAR-T adjuvant (iCTA). Composed of aluminum-manganese hydrogel, iCTA can form a spatially confined antigenic and immunostimulatory niche in-situ. By coupling controlled antigen exposure with STING-type I interferon signaling, iCTA not only recruited and reactivated CAR-T cells, but engage the CAR-negative immunocytes with enhanced dendritic-cell antigen presentation and mobilized endogenous antigen-specific T-cell responses. Combined with mRNA-LNP-mediated in vivo CAR-T generation, a single administration of iCTA increased CAR+ T-cell abundance in draining lymph nodes and blood by 2-fold. It also increased T and NK cell infiltration, established an IFNgamma-enriched tumor microenvironment, and reduced exhaustion-associated T-cell states. iCTA improved tumor regression and survival, establishing an adjuvant strategy to enhance in vivo CAR-T therapy.

bioengineering↗