Biology subjects

Chin, C.-H.

Publications and source records attributed to Chin, C.-H..

3 recordsLinked to original sources

bioRxiv2026

Bispecific VSV-G Engagers: A Platform for Cell-Type-Specific Delivery of Viral Vectors

VSV-G-pseudotyped lentiviral vectors (LVVs) enable highly efficient ex vivo gene delivery through the broadly expressed LDL receptor (LDLR) but lack the cell-type specificity required for in vivo applications. To provide cell-type specificity, we developed reversible engagers consisting of a cell-specific ligand or antibody fused to the ~40-amino-acid VSV-G-binding domains of LDLR. Following endocytosis, the engager dissociates, releasing unmodified VSV-G for efficient delivery of the vector cargo. An engager comprising the CEACAM8 N-terminal domain enables selective transduction of CEACAM6-positive epithelial cells. A trimeric CEACAM8-based engager matching the VSV-G homotrimeric spike blocked non-specific VSV infection through LDLR with an IC50 of 16.7 pM, while enabling effective VSV-mediated lysis of CEACAM6-positive tumor cells. An anti-CD3-based trimeric engager selectively transduced non-preactivated T cells in human PBMCs with high transduction efficiency. Engager-mediated in vivo CAR T cell generation resulted in sustained control of human OPM2 multiple myeloma tumors in NSG mice. This platform may further advance in vivo gene therapy, including in vivo CAR T-cell therapy and tumor-directed oncolytic virotherapy.

cell biology↗

bioRxiv2025

Microbial profiling and single-cell transcriptomics reveal probiotic mechanisms of coral thermal resilience

Probiotics hold promise for enhancing coral resilience under climate-driven thermal stress, yet their mechanisms remain poorly understood. Here, we evaluate two Endozoicomonas species as coral probiotics and characterize their effects on microbial communities and host gene expression. We show that E. acroporae Acr-14T enhances thermal tolerance in Stylophora pistillata, suppresses opportunistic pathogens, and promotes beneficial microbes. To facilitate transcriptomic profiling, we assembled a chromosome-level genome of S. pistillata clade 1 (Pacific lineage) and used it to reveal that E. acroporae Acr-14T mitigates heat-induced protein-folding stress and supports host energy homeostasis. Single-cell transcriptomics further uncovered enhanced pro-survival signaling and modulation of the S-adenosylmethionine (SAMe) synthesis pathway. Together, our findings identify E. acroporae Acr-14T as a robust coral probiotic and provide mechanistic insights into host-microbe interactions that promote coral resilience under thermal stress.

microbiology↗

bioRxiv2025

Unusual Ecofunctional Traits of Endozoicomonas: A Pan-Genomic Perspective

BackgroundEndozoicomonas is a widely distributed genus of marine bacteria, associated with various marine organisms, and recognized for its ecological importance in host health, nutrient cycling, and disease dynamics. Despite its significance, genomic features of Endozoicomonas remain poorly characterized due to limited availability of high-quality genome assemblies. ResultsIn this study, we sequenced 5 novel Endozoicomonas strains and re-sequenced 1 known strain to improve genomic resolution. By integrating these 6 high-quality genomes with 31 others that were publicly available, we identified a distinct, coral-associated clade not recognized by the previous two-clade classification. Pan-genomic analysis revealed significant variation in genetic trait distribution among clades. Notably, Endozoicomonas lacks quorum sensing capabilities, suggesting resistance to quorum quenching mechanisms. It also lacks the ability to synthesize and transport vitamin B12, indicating that it is not a primary source of this nutrient for holobionts. A remarkable feature of Endozoicomonas is its abundance of giant proteins, ranging from 15 to 65 kbp. We identified 92 such proteins, which clustered into three major groups based on amino acid similarity, each associated with specialized functions, such as antimicrobial synthesis, exotoxin production, and cell adhesion. Additionally, we explored prophages and CRISPR-Cas systems. We found that Endozoicomonas acquired prophages from diverse sources via infection or other types of gene transfer. Notably, CRISPR-Cas sequences suggest independent evolutionary trajectories from both prophage acquisition and phylogenetic lineage, implying a potential influence of geographic or environmental pressures. ConclusionsThis study provides new insights into the genomic diversity of Endozoicomonas and its genetic adaptation to diverse hosts. Identification of novel genomic features, including deficiencies in B12 synthesis and quorum sensing, the presence of giant proteins, prophages, and CRISPR-Cas systems, underscores its ecological roles in various holobionts. These findings open new avenues for research on Endozoicomonas and its ecological interactions.

ecology↗