Biology subjects

Wang, P.-N.

Publications and source records attributed to Wang, P.-N..

3 recordsLinked to original sources

bioRxiv2022

Quantum CART (qCART), a piggyBac-based system for development and production of virus-free multiplex CAR-T cell therapy

Chimeric antigen receptor T (CAR-T) cell therapy has the potential to transform cancer treatment. However, CAR-T therapy application is currently limited to certain types of relapsed/refractory B cell lymphomas. To unlock the full potential of CAR-T therapy, technologic breakthroughs will be needed in multiple areas, including optimization of autologous CAR-T development, shortening the innovation cycle, and further manufacturing advancement of next-generation CAR-T therapies. Here, we established a simple and robust virus-free multiplex Quantum CART system that seamlessly and synergistically integrates four platforms: 1. GTailor for rapid identification of lead CAR construct design, 2. Quantum Nufect for effective but gentle electroporation-based gene delivery, 3. Quantum pBac, featuring a virus-free transposon-based vector with large payload capacity and integration profile similar to retrovirus, and 4. iCellar for robust and high-quality CAR+ T memory stem cell expansion. This robust, virus-free multiplex Quantum CART system is expected to unleash the full potential of CAR-T therapy for treating diseases.

cancer biology↗

bioRxiv2022

Quantum pBac: An effective, high-capacity piggyBac-based gene integration vector system for unlocking gene therapy potential

Recent advances in gene therapy have brought novel treatment options for cancer. However, the full potential of this approach has yet to be unlocked due to the safety concerns and limited payload capacity of commonly utilized viral vectors. Virus-free DNA transposons, including piggyBac, have potential to obviate these shortcomings. In this study, we improved a previously developed modified piggyBac system with superior transposition efficiency. We demonstrated that the internal domain sequences (IDS) within the 3 terminal repeat domain of hyperactive piggyBac (hyPB) donor vector contain dominant enhancer elements. Plasmid-free donor vector devoid of IDS was used in conjunction with a helper plasmid expressing Quantum PBase v2 to generate an optimal piggyBac system, Quantum pBac (qPB), for use in T cells. Cells transfected with qPB expressing CD20/CD19 CAR outperformed those transfected with the same donor vector and plasmid expressing hyPB transposase in terms of CAR-T cell production. Importantly, qPB yielded mainly CD8+ CAR-TSCM cells, and the qPB- induced CAR-T cells effectively eliminated CD20/CD19-expressing tumor cells both in vitro and in vivo. Our findings confirm qPB as a promising virus-free vector system with a payload capacity to incorporate multiple genes. This system is highly efficient and potentially safe for mediating transgene integration.

cancer biology↗

bioRxiv2018

Cognitive functions and jugular venous reflux in severe mitral regurgitation

Cardiac diseases with elevated central venous pressure have higher frequency of jugular venous reflux (JVR), which is associated with decreased cerebral blood flow and white matter hyperintensities. Whether patients with severe mitral-regurgitation (SMR) have poorer cognitive functions and whether JVR is involved were determined. Patients with SMR and age/sex-matched controls were prospectively recruited. Neuropsychological tests such as global cognitive (Mini-Mental State Examination, MMSE), verbal memory, executive, and visuospatial domains were performed. Cardiac parameters by cardiac catheterisation and echocardiography, and the frequency of JVR by colour-coded duplex ultrasonography were obtained. Forty patients with SMR and 40 controls (71.1{+/-}12.2, 38-89 years; 75% men) were included. Compared with the controls, patients with SMR had lower scores in all neuropsychological tests but only MMSE and visuospatial test scores were statistically significant after adjusting for age, sex, and educational level. We further adjusted for cardiovascular risk factors; the significance remained in the visuospatial test but diminished in MMSE. Multivariate linear regression analyses adjusted for age, sex, and educational level showed that JVR combined with high right-atrial-pressure (RAP > 50th-percentile, 12 mmHg) was significantly associated with poorer performances in both MMSE [right JVR: B coefficient(95% confidence interval, p)=-2.83(-5.46-0.20, 0.036); left JVR: -2.77(-5.52-0.02, 0.048)] and visuospatial test [right JVR: -4.52(-8.89-0.16, 0.043); left JVR: -4.56(-8.81-0.30, 0.037)], with significances that remained after further adjusting for cardiovascular risk factors. Our results suggest that retrogradely-transmitted venous pressure might be involved in the mechanisms mediating the relationship between cardiac diseases and brain functions.

neuroscience↗