Datta, Payel Publications

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https://hdl.handle.net/20.500.14303/911
ACPHS student authors are denoted by an asterisk (*).

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    Stipulations of cell and gene therapy and the ties to biomanufacturing.
    (Biotechnology Progress, 2025-01-23) Allisha, Justin*; Das, Juthika*; Dunnigan, Thomas*; Sharfstein, Susan T; Datta, Payel
    Cell and gene therapy (CGT) products are emerging and innovative biopharmaceuticals that hold promise for treating diseases that are otherwise beyond the scope of conventional medicines. The evolution of CGT from a research idea to a promising therapeutic product is due to the complementary advancements across various scientific disciplines. First, the innovations and advancements in gene editing and delivery technology have provided fundamental tools to manipulate genes and cells for therapeutic pursuits. Second, advancements in applied and translational research, including how clinical trials are designed, performed, evaluated, and analyzed, have transformed the technology into a potential therapeutic product. Third, advancements in scaling up the production of CGT products have been critical in delivering the product for preclinical studies, clinical trials, and approved treatments. In parallel, regulatory requirements have continuously evolved, with lessons learned from translational studies and biomanufacturing. These combined efforts have transformed CGT products from a promising concept into a reality with the potential to treat a wide range of diseases. However, continued R&D and regulatory oversight are crucial to further improve the safety, efficacy, and accessibility of CGT products.
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    Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin.
    (Glycoconjugate Journal, 2024-12-16) Yang, Jiyuan; Datta, Payel; Xia, Ke; Pomin, Vitor H; Wang, Chunyu; Qiao, Mingqiang; Linhardt, Robert J; Dordick, Jonathan S; Zhang, Fuming
    Dengue viruses (DENV) are transmitted to humans through mosquito bites and infect millions globally. DENV uses heparan sulfate (HS) for attachment and cell entry by binding the envelope protein to highly sulfated HS on target cells. Therefore, inhibiting the binding between DENV and HS could be a promising strategy for preventing DENV infection. In the current study, the interactions between DENV envelope protein (from Type 2 DENV) and heparin (a surrogate for HS) were analyzed using competition solution SPR. Results demonstrate that heparin binds to DENV envelope protein with high affinity (K = 8.83 nM). Competitive Solution SPR assays using surface-immobilized heparin and a series of naturally-sourced and semi-synthetic sulfated glycans demonstrated significant inhibitory activity against the binding of DENV envelope proteins to heparin. This study of molecular interactions could provide insights into the development of therapeutics for DENV infection.
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    Synthesis of bioengineered heparin chemically and biologically similar to porcine-derived products and convertible to low MW heparin.
    (Proceedings of the National Academy of Sciences of the United States of America, 4/2/2024) Douaisi, Marc; Paskaleva, Elena E; Fu, Li; Grover, Navdeep; McManaman, Charity L; Varghese, Sony; Brodfuehrer, Paul R; Gibson, James M; de Joode, Ian; Xia, Ke; Brier, Matthew I; Simmons, Trevor J; Datta, Payel; Zhang, Fuming; Onishi, Akihiro; Hirakane, Makoto; Mori, Daisuke; Linhardt, Robert J; Dordick, Jonathan S
    Heparins have been invaluable therapeutic anticoagulant polysaccharides for over a century, whether used as unfractionated heparin or as low molecular weight heparin (LMWH) derivatives. However, heparin production by extraction from animal tissues presents multiple challenges, including the risk of adulteration, contamination, prion and viral impurities, limited supply, insecure supply chain, and significant batch-to-batch variability. The use of animal-derived heparin also raises ethical and religious concerns, as well as carries the risk of transmitting zoonotic diseases. Chemoenzymatic synthesis of animal-free heparin products would offer several advantages, including reliable and scalable production processes, improved purity and consistency, and the ability to produce heparin polysaccharides with molecular weight, structural, and functional properties equivalent to those of the United States Pharmacopeia (USP) heparin, currently only sourced from porcine intestinal mucosa. We report a scalable process for the production of bioengineered heparin that is biologically and compositionally similar to USP heparin. This process relies on enzymes from the heparin biosynthetic pathway, immobilized on an inert support and requires a tailored -sulfoheparosan with -sulfo levels similar to those of porcine heparins. We also report the conversion of our bioengineered heparin into a LMWH that is biologically and compositionally similar to USP enoxaparin. Ultimately, we demonstrate major advances to a process to provide a potential clinical and sustainable alternative to porcine-derived heparin products.
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    Cholesterol Chip for the Study of Cholesterol-Protein Interactions Using SPR.
    (Biosensors, 9/25/2022) He, Peng; Faris, Shannon; Sagabala, Reddy Sudheer; Datta, Payel; Xu, Zihan; Callahan, Brian; Wang, Chunyu; Boivin, Benoit; Zhang, Fuming; Linhardt, Robert J
    Cholesterol, an important lipid in animal membranes, binds to hydrophobic pockets within many soluble proteins, transport proteins and membrane bound proteins. The study of cholesterol-protein interactions in aqueous solutions is complicated by cholesterol's low solubility and often requires organic co-solvents or surfactant additives. We report the synthesis of a biotinylated cholesterol and immobilization of this derivative on a streptavidin chip. Surface plasmon resonance (SPR) was then used to measure the kinetics of cholesterol interaction with cholesterol-binding proteins, hedgehog protein and tyrosine phosphatase 1B.
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    Anti-SARS-CoV-2 Activity of Rhamnan Sulfate from Monostroma nitidum.
    (Marine Drugs, 11/30/2021) Song, Yuefan; He, Peng; Rodrigues, Andre L; Datta, Payel; Tandon, Ritesh; Bates, John T; Bierdeman, Michael A; Chen, Chen; Dordick, Jonathan; Zhang, Fuming; Linhardt, Robert J
    The COVID-19 pandemic is a major human health concern. The pathogen responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition to ACE2, heparan sulfate (HS) on the surface of host cells also plays a significant role as a co-receptor. Our previous studies demonstrated that sulfated glycans, such as heparin and fucoidans, show anti-COVID-19 activities. In the current study, rhamnan sulfate (RS), a polysaccharide with a rhamnose backbone from a green seaweed, , was evaluated for binding to the S-protein from SARS-CoV-2 and inhibition of viral infectivity in vitro. The structural characteristics of RS were investigated by determining its monosaccharide composition and performing two-dimensional nuclear magnetic resonance. RS inhibition of the interaction of heparin, a highly sulfated HS, with the SARS-CoV-2 spike protein (from wild type and different mutant variants) was studied using surface plasmon resonance (SPR). In competitive binding studies, the IC of RS against the S-protein receptor binding domain (RBD) binding to immobilized heparin was 1.6 ng/mL, which is much lower than the IC for heparin (~750 ng/mL). RS showed stronger inhibition than heparin on the S-protein RBD or pseudoviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, RS showed strong antiviral activities against wild type SARS-CoV-2 and the delta variant.