Biology subjects

Peng, K.-W.

Publications and source records attributed to Peng, K.-W..

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↗

bioRxiv2021

Identification and Validation of N-Acetylputrescine in Combination With Non-Canonical Clinical Features As a Parkinsons Disease Biomarker Panel

Parkinsons disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group with variable motor and non-motor symptoms with a degree of misdiagnosis. Only 3-5% of sporadic Parkinsons patients present with genetic abnormalities, thus environmental, metabolic, and other unknown causes contribute to the pathogenesis of Parkinsons disease, which highlights the critical need for biomarkers. There could be a significant clinical benefit to treating Parkinsons disease at the earliest stage and identify at-risk populations once disease-modifying treatments are available. In the present study, we prospectively collected and analyzed plasma samples from 201 Parkinsons disease patients and 199 age-matched non-diseased controls. Multiomic and Bayesian artificial intelligence analysis of molecular and clinical data identified the diagnostic utility of N-acetyl putrescine (NAP) in combination with smell (B-SIT), depression/anxiety (HADS), and acting out dreams (RBD1Q) clinical measurements. The clinical and biomarker panel demonstrated an area under the curve, AUC = 0.9, positive predictive value, PPV = 0.91, and negative predictive value, NPV = 0.66 utilizing all four variables. The assessed diagnostic panel demonstrates combinatorial utility in diagnosing Parkinsons disease, allowing for an integrated interpretation of disease pathophysiology and highlighting the use of multi-tiered panels in neurological disease diagnosis.

neuroscience↗

bioRxiv2020

Development and validation of IMMUNO-COV: a high-throughput clinical assay for detecting antibodies that neutralize SARS-CoV-2

We here describe the development and validation of IMMUNO-COV, a high-throughput clinical test to quantitatively measure SARS-CoV-2-neutralizing antibodies, the specific subset of anti-SARS-CoV-2 antibodies that block viral infection. The test measures the capacity of serum or purified antibodies to neutralize a recombinant Vesicular Stomatitis Virus (VSV) encoding the SARS-CoV-2 spike glycoprotein. This recombinant virus (VSV-SARS-CoV-2-S-{Delta}19CT) induces fusion in Vero cell monolayers, which is detected as luciferase signal using a dual split protein (DSP) reporter system. VSV-SARS-CoV-2-S-{Delta}19CT infection was blocked by monoclonal -SARS-CoV-2-spike antibodies and by plasma or serum from SARS-CoV-2 convalescing individuals. The assay exhibited 100% specificity in validation tests, and across all tests zero false positives were detected. In blinded analyses of 230 serum samples, only two unexpected results were observed based on available clinical data. We observed a perfect correlation between results from our assay and 80 samples that were also assayed using a commercially available ELISA. To quantify the magnitude of the anti-viral response, we generated a calibration curve by adding stepped concentrations of -SARS-CoV-2-spike monoclonal antibody to pooled SARS-CoV-2 seronegative serum. Using the calibration curve and a single optimal 1:100 serum test dilution, we reliably measured neutralizing antibody levels in each test sample. Virus neutralization units (VNUs) calculated from the assay correlated closely (p < 0.0001) with PRNTEC50 values determined by plaque reduction neutralization test against a clinical isolate of SARS-CoV-2. Taken together, these results demonstrate that the IMMUNO-COV assay accurately quantitates SARS-CoV-2 neutralizing antibodies in human sera and therefore is a potentially valuable addition to the currently available serological tests. The assay can provide vital information for comparing immune responses to the various SARS-CoV-2 vaccines that are currently in development, or for evaluating donor eligibility in convalescent plasma therapy studies.

immunology↗