A5049039755- Transgenic Plants and Applications
- Plant tissue culture and regeneration
- Glycosylation and Glycoproteins Research
- Plant Virus Research Studies
- Toxin Mechanisms and Immunotoxins
- Escherichia coli research studies
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Protein Hydrolysis and Bioactive Peptides
- CRISPR and Genetic Engineering
- Viral Infectious Diseases and Gene Expression in Insects
- Hepatitis B Virus Studies
- Endoplasmic Reticulum Stress and Disease
- Clostridium difficile and Clostridium perfringens research
- HIV/AIDS Research and Interventions
- Immune Cell Function and Interaction
- Hepatitis C virus research
- Neuropeptides and Animal Physiology
- Insect Utilization and Effects
- Reproductive tract infections research
- Galectins and Cancer Biology
- Immunotherapy and Immune Responses
- Vibrio bacteria research studies
- Nutrition, Genetics, and Disease
- Carbohydrate Chemistry and Synthesis
University of Louisville
2016-2025
University of Louisville Hospital
2024
University of Alabama at Birmingham
2022
SRI International
2022
James Graham Brown Foundation
2009-2020
Bioengineering Center
2017
National Center for Genetic Engineering and Biotechnology
2017
John Wiley & Sons (United States)
2017
Owensboro Health
2010-2016
Arizona State University
2004-2016
Abstract Many kinds of bioactive peptides which might prevent lifestyle‐related diseases are released from food proteins after enzymatic digestion. Inhibitory for angiotensin I‐converting enzyme (ACE) having anti‐hypertensive effect have been isolated digests various proteins. LKPNM, was the thermolysin digest dried bonito activated 8‐fold by ACE itself and showed a prolonged oral administration. Two vasorelaxing peptides, ovokinin ovokinin(2–7), showing antihypertensive administration were...
Membrane-bound oligosaccharides form the interfacial boundary between cell and its environment, mediating processes such as adhesion signaling. These structures can undergo dynamic changes in composition expression based on type, external stimuli, genetic factors. Glycosylation, therefore, is a promising target of therapeutic interventions for presently incurable forms advanced cancer. Here, we show that cholangiocarcinoma metastasis characterized by down-regulation Golgi α-mannosidase I...
In this report, we deal with the isolation of a novel vasorelaxing peptide from chymotryptic digest ovalbumin and its activities. This is composed Arg‐Ala‐Asp‐His‐Pro‐Phe (RADHPF) in sequence, corresponding to residues 359–364 ovalbumin. (30–300 μM) exerted dose‐dependent vasodilation an isolated mesenteric artery spontaneously hypertensive rat which was pre‐constricted by phenylephrine, besides relaxation being endothelium‐dependent. It noteworthy that nitric oxide synthase inhibitor N G...
Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since NLG are also found some host proteins it is possible treatment with antiviral may trigger undesirable side effects. For other concanavalin A, banana and cyanovirin-N (CV-N), interactions between yet undescribed cellular moieties been reported...
Plant molecular farming (PMF) is rapidly gaining traction as a viable alternative to the currently accepted paradigm of producing biologics. While platform potentially cheaper and more scalable than conventional manufacturing systems, expression yields appropriate post-translational modifications along plant secretory pathway remain challenge for certain proteins. Viral fusion glycoproteins in particular are often expressed at low plants and, some cases, may not be appropriately processed....
Plant-based transient overexpression systems enable rapid and scalable production of subunit vaccines. Previously, we have shown that cholera toxin B (CTB), an oral vaccine antigen, is N-glycosylated upon expression in transgenic Nicotiana benthamiana. Here, found aglycosylated CTB by agroinfiltration a tobamoviral vector causes massive tissue necrosis poor accumulation unless retained the endoplasmic reticulum (ER). However, re-introduction N-glycosylation to its original or alternative...
Introduction Cholera toxin B subunit (CTB) is a component of an internationally licensed oral cholera vaccine. The protein induces neutralizing antibodies against the holotoxin, virulence factor responsible for severe diarrhea. A field clinical trial has suggested that addition CTB to killed whole-cell bacteria provides superior short-term protection whole-cell-only vaccines; however, challenges in biomanufacturing (i.e., cost and scale) hamper its implementation mass vaccination developing...
High-mannose-type glycans (HMGs) are aberrantly enriched on HIV envelope glycoproteins. However, there is currently no drug selectively targeting HIV-associated HMGs. Here, we describe a novel HMG-targeting "lectibody," recombinant Fc-fusion protein comprising human IgG1 Fc and actinohivin lectin variant (Avaren) obtained by structure-guided modifications for improved overall surface charge properties (AvFc). AvFc was engineered produced using rapid scalable plant-based transient...
Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. Here, we showed that lectibody consisting the high-mannose glycan-binding lectin Avaren and human immunoglobulin G1 (IgG1) Fc (AvFc) selectively recognizes range cell lines derived from lung, breast, colon, blood cancers at nanomolar concentrations. Binding AvFc to non-small lung (NSCLC) A549 H460 was characterized in detail. Co-immunoprecipitation proteomics...
Postinfiltration air temperature is known to affect the accumulation of recombinant protein in Agrobacterium-mediated transient expression Nicotiana benthamiana plants, including number days needed reach maximum content and rate reduction thereafter. This study aimed clarify whether transcript levels transgenes those plant stress response markers (i.e., hypersensitive endoplasmic reticulum [ER] stress) could be primary determinants influenza hemagglutinin (HA) at 21 or 26°C. We found no...
Background/Objectives: EPICERTIN, a biotherapeutic candidate for mucosal healing in inflammatory bowel disease (IBD) and other disorders, was subjected to an extensive long-term stability program evaluate its molecular physicochemical properties. Additionally, forced degradation assessment conducted identify EPICERTIN's products under various conditions, including thermal stress, pH variations, agitation, oxidation. Methods: The of EPICERTIN drug substance (DS), formulated phosphate-buffered...
A vaccine that would engage the mucosal immune system against a broad range of HIV-1 subtypes and prevent epithelial transmission is highly desirable. Here we report fusing targeting B subunit cholera toxin to conserved galactosylceramide-binding domain (including ELDKWA-neutralizing epitope) gp41 envelope protein, which mediates transcytosis across epithelia. Chimeric protein expressed in bacteria or plants assembled into oligomers were capable binding galactosyl-ceramide G M1 gangliosides....
Despite current prophylactic strategies, sexually transmitted infections (STIs) remain significant contributors to global health challenges, spurring the development of new multipurpose delivery technologies protect individuals from and treat virus infections. However, there are few methods currently available prevent no method date that cures human immunodeficiency (HIV) infection or combinations STIs. While oral topical preexposure prophylaxes have protected against HIV infection, they...
The potent anti‐hypertensive peptide, RPLKPW, has been designed based on the structure of ovokinin(2–7). sequence encoding this peptide was introduced into three homologous sites in gene for soybean β‐conglycinin α′ subunit. native subunit as well modified, RPLKPW‐containing were expressed Escherichia coli , recovered from soluble fraction and then purified by ion‐exchange chromatography. RPLKPW released recombinant after vitro digestion trypsin chymotrypsin. Moreover, undigested given...
Ovokinin(2-7) (RADHPF), an orally active anti-hypertensive peptide derived from ovalbumin, lowers blood pressure in SHRs at a dose of 10 mg/kg. Attempts were made to potentiate its activity by replacing the amino acid residues [Pro2, Phe3]-ovokinin(2-7), which was previously reported have 33-fold stronger than ovokinin(2-7). The Phe3]-ovokinin(2-7) improved replacement C-terminal Phe residue with Trp. Then, best other positions for effect selected. RPLKPW, most potent derivative obtained,...
Plants are potentially the most economical platforms for large-scale production of recombinant proteins. Thus, plant-based expression subunit human immunodeficiency virus type 1 (HIV-1) vaccines provides an opportunity their global use against acquired syndrome pandemic. CTB-MPR(649-684)[CTB, cholera toxin B subunit; MPR, membrane proximal (ectodomain) region gp41] is HIV-1 vaccine candidate that has been shown previously to induce antibodies block a pathway mucosal transmission. In this...
Broadly neutralizing monoclonal antibodies (bnMAbs) may offer powerful tools for HIV-1 preexposure prophylaxis, such as topical microbicides. However, this option is hampered due to expensive MAb biomanufacturing based on mammalian cell culture. To address issue, we developed a new production system bnMAb VRC01 in Nicotiana benthamiana plants using tobamovirus replicon vector. Unlike conventional two-vector-based expression, was designed overexpress full-length IgG1 from single polypeptide...
Cholera toxin B subunit (CTB) is a component of licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that administration in mice plant-made recombinant (CTBp) significantly increased several immune cell populations colon lamina propria. Global gene expression analysis revealed CTBp had more pronounced than small intestine, with significant activation TGFβ-mediated pathways epithelium. The...
Cervical cancer is the most common malignancy among women particularly in developing countries, with human papillomavirus (HPV) 16 causing 50% of invasive cervical cancers. A plant-based HPV vaccine an alternative to currently available virus-like particle (VLP) vaccines, and would be much less expensive. We optimized methods express HPV16 L1 protein purify VLPs from tobacco (Nicotiana benthamiana) leaves transfected magnICON deconstructed viral vector expression system. proteins were...