A5022788010- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Hepatitis C virus research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- ATP Synthase and ATPases Research
- Health and Medical Research Impacts
- Alzheimer's disease research and treatments
- Palliative Care and End-of-Life Issues
- RNA Interference and Gene Delivery
- Drug Transport and Resistance Mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Ubiquitin and proteasome pathways
- Cardiac pacing and defibrillation studies
- Nicotinic Acetylcholine Receptors Study
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Advanced Proteomics Techniques and Applications
- Advances in Oncology and Radiotherapy
- HIV/AIDS Research and Interventions
- Heart Failure Treatment and Management
- Virus-based gene therapy research
Community Care
2022
Bristol-Myers Squibb (United States)
2017-2018
Pfizer (United States)
2011
Mercy Medical Center
2010
Mercy Medical Center North Iowa
2010
Howard Hughes Medical Institute
2003
Brigham and Women's Hospital
2003
Harvard University
2003
Abstract High‐throughput screening (HTS) of chromatography resins for identifying optimal protein purification conditions is becoming an integral part industrial process development. In this work, ceramic hydroxyapatite (cHA) 15 humanized monoclonal antibodies (mAbs) was examined by HTS. MAb binding, as quantified partition coefficient ( K p ), measured under 92 combinations sodium chloride, phosphate, and pH. Binding varied inversely with these variables all mAbs tested. However, the...
Infection of T lymphocytes by the cytopathic retrovirus feline leukemia virus subgroup (FeLV-T) requires FeLIX, a cellular coreceptor that is encoded an endogenous provirus and closely resembles receptor-binding domain (RBD) B (FeLV-B). We determined structure FeLV-B RBD, which has FeLIX activity, to 2.5-A resolution X-ray crystallography. The receptor-specific subdomain this glycoprotein differs dramatically from Friend murine (Fr-MLV), binds different cell surface receptor. Remarkably, we...
A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated using in vitro selection. This binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at step after engagement preceding membrane fusion. The progenitor sequence of this selected from library trillions Adnectin variants mRNA display then further optimized for improved antiviral physical properties. final exhibited full potency against panel 124 envelope (gp160) proteins spanning 11 subtypes,...
Long-acting antiretrovirals could provide a useful alternative to daily oral therapy for HIV-1-infected individuals. Building on bi-specific molecule with adnectins targeting CD4 and gp41, potential long-acting biologic, GSK3732394, was developed three independent synergistic modes of HIV entry inhibition that potentially be self-administered as subcutaneous injection. Starting the inhibitor, an α-helical peptide inhibitor optimized linked anti-gp41 adnectin, each separate exhibiting at...
Temsavir binds directly to the HIV-1 envelope glycoprotein gp120 and selectively inhibits interactions between CD4 receptors. Previous studies identified amino acid positions where substitutions are associated with reduced susceptibility temsavir. The mechanism by which temsavir is altered in these glycoproteins was evaluated. Pseudoviruses encoding alone (S375H/I/M/N, M426L, M434I, M475I) or combination (S375H + were engineered on a wild-type JRFL background. Temsavir-gp120 CD4-gp120...
The HIV-1 maturation inhibitor (MI) VH3739937 (VH-937) inhibits cleavage between capsid and spacer peptide 1 exhibits an oral half-life in humans compatible with once-weekly dosing. Here, the antiviral properties of VH-937 are described. exhibited potent activity against all laboratory strains, clinical isolates, recombinant viruses examined, half-maximal effective concentration (EC50) values ≤ 5.0 nM. In multiple-cycle assays, less susceptible to other MIs, including A364V, were inhibited...
During ongoing C-type retrovirus infection, the probability of leukemia caused by insertional gene activation is markedly increased emergence recombinant retroviruses that repeatedly infect host cells. The murine mink cell focus-inducing (MCF) viruses with this property have acquired characteristic changes in N-terminal domain their envelope glycoprotein specify binding to a different receptor than parental ecotropic virus. In report, we show MCF virus infection occurs through (termed Syg1)...
The N17 region of gp41 in HIV-1 is the most conserved gp160. mRNA selection technologies were used to identify an adnectin that binds this and inhibits gp41-induced membrane fusion. Additional conditions optimize greater potency (5.4 ± 2.6 nM) against improved binding affinity for N17-containing helical trimer (0.8 0.4 nM). Resistance mapped a single Glu-to-Arg change within coding region. optimized (6200_A08) exhibited high broad-spectrum activity 123 envelope proteins multiple clinical...
The Na<sub>V</sub>1.7 voltage-gated sodium channel is implicated in human pain perception by genetics. Rare gain of function mutations lead to spontaneous humans whereas loss results congenital insensitivity pain. Hence, agents that specifically modulate the have potential yield novel therapeutics treat complexity and challenges generate recombinant cell lines with high expression led a surrogate target strategy approach employing chimeras bacterial Na<sub>V</sub>Ab. In this report we...
To characterize the in vitro binding and effector function properties of CD20-directed small modular immunopharmaceutical (SMIP) 2LM20-4, to compare its vivo B-cell depletion activity with mutated 2LM20-4 P331S [no complement-dependent cytotoxicity (CDC)] rituximab cynomolgus monkeys.Direct is examined flow cytometry, confocal microscopy, scatchard lipid raft assays. Effector assays include CDC Fc-mediated cellular toxicity. In 6-month-long study, single i.v. dosages 1 or 10 mg/kg anti-CD20...
Background The GSK3732394 multivalent protein was developed as a novel, long-acting, antiretroviral biologic treatment regimen with three independent, non–cross-resistant mechanisms for inhibiting HIV-1 entry. Methods A single-centre, Phase 1, double-blind, randomized, placebo-controlled study conducted in healthy volunteers, using 2-part adaptive design: Part participants were randomized to receive subcutaneous injection of or placebo (3:1) single ascending doses (10-mg starting dose); 2,...