A major challenge in gene therapy for GJB2-related hearing loss (DFNB1), the most common form of hereditary deafness, is achieving efficient and precise connexin 26 delivery. Herein, we engineered two cell type-specific promoters (GJB2-1 and WFS1-2274) and developed an AAV capsid, AAV-MAS012, with enhanced transduction efficiency in mature cochlear cells. Our AAV-mediated gene therapy systems […]
Longitudinal per-lesion in vivo imaging reveals allele-dependent resistance evolution in EGFR-mutant lung cancer
Acquired resistance to targeted therapies remains an inevitable outcome in EGFR-mutant non-small cell lung cancer, yet the spatiotemporal dynamics through which resistant clones emerge and evolve in vivo remain incompletely understood. In particular, how distinct oncogenic EGFR alleles shape evolutionary trajectories under therapeutic pressure within native tumor microenvironments remains unclear. Here, we establish a longitudinal […]
Recombinant measles virus equipped with BNiP3, a pro-apoptotic gene, targets β-catenin pathway in triple negative breast cancer cells
Oncolytic virotherapy is an emerging cancer therapy using genetically modified viruses. We previously reported engineering of measles virus with BNiP3, a proapoptotic gene for oncolytic purposes. The recombinant virus had shown promising results in breast cancer cells with a bias towards TNBC, an invasive and an aggressive subtype. Here, we investigated the mechanistic insights of […]
Ocular findings in Northern Gannets following an outbreak of high pathogenicity avian influenza (H5N1)
During 2021-2022, high pathogenicity avian influenza (HPAI) caused mass mortality in wild birds across Europe, with Northern Gannets (Morus bassanus) among the most affected. Following the outbreak, unusual alterations in the species’ characteristic pale iris were observed in some individuals. Opportunistically captured gannets on Bass Rock (n=52), selected to represent a range of iris pigmentation, […]
How Functional Variants Reconfigure the Rac2 Conformational Landscape
Rac2, a member of the Rho family of small GTPases, is a fundamental regulator of essential cellular processes. Pathogenic substitutions near and within the Switch II region, specifically D57N and E62K, have been implicated in oncogenesis and immunodeficiency. Despite their proximity, D57N is characterized as a loss-of-function mutation, while E62K is a constitutively active, gain-of-function […]
SIRPA suppresses integrin-dependent virus endocytosis
New World arenaviruses (NWAs) that cause viral hemorrhagic fever, such as Junin virus, have few therapeutic options. Entry of these viruses into cells is mediated by binding to cell surface receptors, followed by endocytosis and trafficking to a low pH compartment. We showed previously that Signal Regulatory Protein Alpha (SIRPA), a critical cell surface receptor […]
Conjugation-based genome engineering enables rapid prototyping and bioproduction in non-model bacteria
Non-model bacteria offer unique metabolic capabilities for sustainable bioproduction, yet their limited genetic accessibility hinders systematic strain development. Here we present conjugation-based serine recombinase-assisted genome engineering (cSAGE), a broad-host-range platform that enables predictable, iterative genomic integration in transformation-resistant bacteria. cSAGE combines conjugative DNA delivery, standardized low-copy vectors, orthogonal recombinases, and modular genetic parts to support […]
Extensive opsin gene expansion and non-cerebral origin of the minimalist eye in a model tardigrade
Panarthropod vision exhibits extraordinary morphological and functional diversity, yet the sensory biology of tardigrades–microscopic extremophiles renowned for their resilience–remains poorly understood. In the model tardigrade Hypsibius exemplaris, we uncover an unprecedented expansion of opsin genes, with over 100 paralogs constituting the largest known opsin repertoire in any animal. Paradoxically, the visual system is structurally minimalist: […]
Deep FLASH-seq profiling of purified canine sensory neurons uncovers species-specific signatures relevant to pain and itch
Naturally occurring pain and itch disorders in the domestic dog represent an important and underexploited opportunity for translational sensory neuroscience. These conditions largely mirror human disease, highlighting the need for detailed comparative understanding of canine somatosensory neurobiology. Here, we present a single-cell transcriptomic characterisation of the canine dorsal root ganglion (DRG), providing molecular insights into […]
The Origin and Migration of the Ameru Community in Kenya based on mtDNA analysis.
Human diversity did not only remain restricted to their socio-cultural and linguistic domains but also have penetrated deep inside their genetic root. Africa harbors more genetic diversity than any other part of the world. Diversification of the African lineages were complex, involving long-distance gene flow. Data from Africansis needed to better understand the origin and […]
Mechanism of HIV-1 Capsid Rupture and Uncoating by Reverse Transcription
One of the key events in the HIV-1 life cycle is reverse transcription, during which single-stranded viral RNA (ssRNA) is converted into double-stranded DNA (dsDNA). This process occurs inside the mature virus capsid and, once it reaches a critical threshold, drives capsid rupture. This uncoating is essential for infection because it releases viral genetic material […]
Efficient exploration of peptide libraries using active learning with AlphaFold-based screening
We previously showed that AlphaFold2 can be used to screen for peptide-binding epitopes targeting the extraterminal (ET) domain of Bromodomain and Extraterminal (BET) proteins from candidate protein partners identified in pull-down experiments. However, such approaches require large numbers of AlphaFold2 calculations, making exhaustive screening impractical for larger datasets, such as viral proteomes that may target […]