Works (25)
Updated: February 21st, 2024 05:01
2024 article
Engineering a "muco-trapping" ACE2-immunoglobulin hybrid with picomolar affinity as an inhaled, pan-variant immunotherapy for COVID-19
Tiruthani, K., Cruz-Teran, C., Chan, J. F. W., Ma, A., Mcsweeney, M., Wolf, W., … Lai, S. K. (2024, February 7). BIOENGINEERING & TRANSLATIONAL MEDICINE.
author keywords: ACE2; antibody; COVID-19; drug delivery; immunodecoy; inhaled delivery; monoclonal antibody; SARS-CoV-2
TL;DR:
ACE2‐(G4S)6‐Fc effectively trapped fluorescent SARS‐CoV‐2 virus like particles in fresh human airway mucus and was stably nebulized using a commercial vibrating mesh nebulizer, supporting further development of ACE2‐(G4S)6‐Fc as an inhaled immunotherapy for COVID‐19, as well as other emerging viruses that bind ACE2 for cellular entry.
(via Semantic Scholar)
open access via onlinelibrary.wiley.com (publisher PDF)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: February 19, 2024
2023 journal article
Modeling identifies variability in SARS-CoV-2 uptake and eclipse phase by infected cells as principal drivers of extreme variability in nasal viral load in the 48 h post infection
JOURNAL OF THEORETICAL BIOLOGY, 565.
author keywords: SARS-CoV-2; Nasal infection; Viral load; Mechanistic modeling
MeSH headings : Humans; SARS-CoV-2 / genetics; COVID-19; RNA, Viral / genetics; Viral Load; COVID-19 Testing
TL;DR:
Naval viral load sensitivity arising from the timing of sample collection relative to onset of infection and from heterogeneity in the kinetics of cellular infection, uptake, replication, and shedding of viral RNA copies is focused on.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: May 9, 2023
2022 journal article
A PBPK model recapitulates early kinetics of anti-PEG antibody-mediated clearance of PEG-liposomes
JOURNAL OF CONTROLLED RELEASE, 343, 518–527.
author keywords: PBPK model; Polyethylene glycol; PEGylated liposomes; Accelerated blood clearance; Anti-PEG antibodies
MeSH headings : Animals; Antibodies; Kinetics; Liposomes; Mice; Polyethylene Glycols / pharmacokinetics; Positron Emission Tomography Computed Tomography; Tissue Distribution
TL;DR:
A physiologically based pharmacokinetic (PBPK) model designed to resolve APA's impact on both early- and late-phase pharmacokinetics and biodistribution of intravenously administered PEGylated drugs is developed.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: May 23, 2022
2022 article
Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19
McSweeney, M., Stewart, I., Richardson, Z., Kang, H., Park, Y., Kim, C., … Lai, S. (2022, August 30). BIOENGINEERING & TRANSLATIONAL MEDICINE.
author keywords: antiviral; COVID-19; drug delivery; inhaled delivery; mAb; nebulization
TL;DR:
It is shown that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries around the world, can effectively trap Sars-CoV-2 virus-like-particles in fresh human airway mucus and substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-Cov-2 and other respiratory pathologies.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: September 12, 2022
2021 journal article
Bispecific binder redirected lentiviral vector enables in vivo engineering of CAR-T cells
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 9(9).
author keywords: immunotherapy; cell engineering; receptors; chimeric antigen; antibody specificity
MeSH headings : Animals; Antibodies, Bispecific / metabolism; Disease Models, Animal; Humans; Lentivirus / pathogenicity; Mice; Receptors, Chimeric Antigen / metabolism; Tissue Engineering / methods
TL;DR:
In vivo engineering of CAR-T cells is engineered directly in vivo by administering a lentivirus expressing a mutant Sindbis envelope, coupled with a bispecific antibody binder that redirects the virus to CD3+ human T cells that markedly control the growth of an aggressive pre-established xenograft B cell tumor.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: October 4, 2021
2021 journal article
Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception
SCIENCE TRANSLATIONAL MEDICINE, 13(606).
MeSH headings : Animals; Contraception; Female; Humans; Immunoglobulin Fab Fragments; Immunoglobulin G; Male; Pregnancy; Sheep; Sperm Motility; Spermatozoa
TL;DR:
Motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of Immunoglobulin G (IgG), a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm are developed.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: August 30, 2021
2021 journal article
Experimental Data and PBPK Modeling Quantify Antibody Interference in PEGylated Drug Carrier Delivery
BULLETIN OF MATHEMATICAL BIOLOGY, 83(12).
author keywords: PBPK model; Latin hypercube sampling; Parameter optimization; Anti-PEG antibodies; PEGylated liposomes
MeSH headings : Animals; Drug Carriers; Mathematical Concepts; Mice; Models, Biological; Polyethylene Glycols / pharmacokinetics; Positron Emission Tomography Computed Tomography; Tissue Distribution
TL;DR:
Near-continuous experimental measurements of PL concentration during the first hour post-injection from the liver, spleen, kidney, muscle, lung, and blood plasma, are used as truth sets with LHS to infer optimal parameter ranges for the full PBPK model.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: November 23, 2021
2021 journal article
High MW polyethylene glycol prolongs circulation of pegloticase in mice with anti-PEG antibodies
JOURNAL OF CONTROLLED RELEASE, 338, 804–812.
author keywords: Pegloticase; PEG; Anti-PEG antibodies
MeSH headings : Animals; Gout; Humans; Mice; Polyethylene Glycols; Tissue Distribution; Urate Oxidase; Uric Acid
TL;DR:
The use of 40 kDa free PEG to restore the circulation of radio-labeled pegloticase in mice using longitudinal Positron Emission Tomography (PET) imaging over 4 days suggests that pre-infusion of free P EG may be a promising strategy to enable the safe and efficacious use of peglosis and other PEGylated drugs in patients that have previously failed therapy due to induced APA.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: October 26, 2021
2021 article
The biophysical principles underpinning muco-trapping functions of antibodies
Schaefer, A., & Lai, S. K. (2021, June 26). HUMAN VACCINES & IMMUNOTHERAPEUTICS.
author keywords: Passive immunization; antibodies; mucus
MeSH headings : Antibody-Dependent Cell Cytotoxicity; Immunoglobulin G; Mucins; Mucus / metabolism
TL;DR:
The mechanism by which the accumulation of weak Fc-mucin bonds by IgG bound to the surface of a pathogen can result in immobilization of antibody-pathogen complexes, and how trapping in mucus can contribute to protection against foreign pathogens are provided.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: August 2, 2021
2020 journal article
Antibody-mediated trapping in biological hydrogels is governed by sugar-sugar hydrogen bonds
ACTA BIOMATERIALIA, 107, 91–101.
author keywords: Biological hydrogels; Glycosylation; Antibodies; Hydrogen bonds
MeSH headings : Alginates / chemistry; Chitosan / chemistry; Hydrogels / chemistry; Hydrogen Bonding; Immunoglobulin G / immunology; Immunoglobulin G / metabolism; Immunoglobulin M / immunology; Immunoglobulin M / metabolism; Nanoparticles / chemistry; Polyethylene Glycols / chemistry; Polyethylene Glycols / metabolism; Polystyrenes / chemistry; Protein Binding; Sepharose / chemistry
TL;DR:
A model in which hydrogen bonding between carboxyl and hydroxyl groups of glycans on both Ab and matrix facilitates Ab-mediated trapping of pathogens in biogels is proposed, which offers a blueprint for designing de novo hydrogels that could harness Ab-matrix interactions for various biomedical and biological applications.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: May 8, 2020
2020 review
Challenges & opportunities for phage-based in situ microbiome engineering in the gut
[Review of Challenges & opportunities for phage-based in situ microbiome engineering in the gut]. JOURNAL OF CONTROLLED RELEASE, 326, 106–119.
author keywords: Bacteriophage; Phage; Microbiome; Microbiome engineering; in situ engineering; Microbiome gene therapy
MeSH headings : Bacteria; Bacteriophages; Gastrointestinal Microbiome; Humans; Microbiota
TL;DR:
The challenges and opportunities associated with engineering bacteriophages to control and manipulate the gut microbiome are presented and areakin to human gene therapies delivered by viral vectors.
(via Semantic Scholar)
Source: Web Of Science
Added: October 12, 2020
2020 review
Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy
[Review of ]. ADVANCED DRUG DELIVERY REVIEWS, 169, 100–117.
MeSH headings : Angiotensin-Converting Enzyme 2 / antagonists & inhibitors; Angiotensin-Converting Enzyme 2 / metabolism; Animals; Antibodies, Monoclonal / chemistry; Antibodies, Monoclonal / metabolism; Antibodies, Monoclonal / therapeutic use; Antiviral Agents / chemistry; Antiviral Agents / metabolism; Antiviral Agents / therapeutic use; COVID-19 / diagnosis; COVID-19 / metabolism; COVID-19 / therapy; Humans; Immunization, Passive; Immunologic Factors / chemistry; Immunologic Factors / metabolism; Immunologic Factors / therapeutic use; Protein Structure, Secondary; Protein Structure, Tertiary; SARS-CoV-2 / chemistry; SARS-CoV-2 / drug effects; SARS-CoV-2 / metabolism; Virus Shedding / drug effects; Virus Shedding / physiology; COVID-19 Serotherapy
TL;DR:
The mechanism by which SARS-CoV-2 and similar viruses spread within the lung is investigated, along with available biodistribution data for systemically injected mAb, and the evidence supporting inhaled delivery of antiviral mAb as an early intervention against COVID-19 that could prevent important pulmonary morbidities associated with the infection.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: March 15, 2021
2020 journal article
Engineering tetravalent IgGs with enhanced agglutination potencies for trapping vigorously motile sperm in mucin matrix
ACTA BIOMATERIALIA, 117, 226–234.
author keywords: Agglutination; Antibodies; Antibody engineering; Contraception; Sperm; Tetravalent IgG
MeSH headings : Agglutination; Antibodies; Female; Humans; Male; Mucins; Sperm Agglutination; Spermatozoa
TL;DR:
Tetravalent IgG constructs engineered to bind a ubiquitous sperm antigen using a Fab previously isolated from an immune infertile woman offer promise for non-hormonal contraception and underscores the multimerization of IgG as a promising strategy to enhance antibody effector functions based on immune exclusion.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
10. Reduced Inequalities
(OpenAlex)
Source: Web Of Science
Added: November 30, 2020
2020 journal article
LPS-binding IgG arrests actively motile Salmonella Typhimurium in gastrointestinal mucus
MUCOSAL IMMUNOLOGY, 13(5), 814–823.
MeSH headings : Animals; Antibodies, Bacterial / immunology; Disease Models, Animal; Immunoglobulin Fab Fragments / immunology; Immunoglobulin Fc Fragments / immunology; Immunoglobulin G / immunology; Intestinal Mucosa; Lipopolysaccharides / immunology; Mice; Mucus / immunology; Mucus / microbiology; Polysaccharides / immunology; Protein Binding / immunology; Salmonella Infections / immunology; Salmonella Infections / microbiology; Salmonella typhimurium / immunology
TL;DR:
The addition of anti-lipopolysaccharide IgG to GI mucus markedly reduced the progressive motility of Salmonella by lowering the swim speed and retaining individual bacteria in an undirected motion state, implicate IgG-mucin crosslinking as a broadly conserved function that reduces mucous penetration of both bacterial and viral pathogens.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
14. Life Below Water
(OpenAlex)
Source: Web Of Science
Added: March 23, 2020
2020 journal article
Learning from past failures: Challenges with monoclonal antibody therapies for COVID-19
JOURNAL OF CONTROLLED RELEASE, 329, 87–95.
MeSH headings : Administration, Inhalation; Antibodies, Monoclonal / administration & dosage; Antibodies, Monoclonal / therapeutic use; Antibodies, Neutralizing / immunology; Antibodies, Viral / immunology; Antiviral Agents / administration & dosage; Antiviral Agents / therapeutic use; Humans; Immunotherapy / methods; Injections, Intravenous; Nebulizers and Vaporizers; SARS-CoV-2 / drug effects; Secondary Prevention; Treatment Outcome; COVID-19 Drug Treatment
TL;DR:
Prior efforts to advance antiviral mAbs for other acute respiratory infections (ARIs) are analyzed to highlight the challenges faced by mAb-based immunotherapies for COVID-19, and evidence supporting early intervention immediately following a positive diagnosis via inhaled delivery of mAbs with vibrating mesh nebulizers is presented.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: June 10, 2021
2020 journal article
Pre-treatment with high molecular weight free PEG effectively suppresses anti-PEG antibody induction by PEG-liposomes in mice
JOURNAL OF CONTROLLED RELEASE, 329, 774–781.
author keywords: Polyethylene glycol antibodies; Anti-PEG antibodies; PEGylation; Polyethylene glycol; Anti-drug antibodies; Drug delivery; Accelerated blood clearance; Nanoparticles; Tolerogenesis
MeSH headings : Animals; Humans; Liposomes; Mice; Polyethylene Glycols
TL;DR:
Surprisingly, it is found that a single administration of free PEG alone was capable of markedly reducing the APA response to PEG-liposomes for ~2 months; the effectiveness was comparable to, and frequently exceeded, interventions with different tolerogenic P EG- Liposomes.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: June 10, 2021
2020 journal article
Structure of an anti-PEG antibody reveals an open ring that captures highly flexible PEG polymers
COMMUNICATIONS CHEMISTRY, 3(1).
TL;DR:
Crystal structures of an anti-PEG antibody binding fragment bound to PEG are reported and key binding residues are identified by site-directed mutagenesis to illustrate a strategy by which antibodies can bind highly flexible repeated structures that lack fixed conformations, such as polymers.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: September 28, 2020
2020 journal article
The cervicovaginal mucus barrier to HIV-1 is diminished in bacterial vaginosis
PLOS PATHOGENS, 16(1).
MeSH headings : Adult; Bacteria / classification; Bacteria / genetics; Bacteria / isolation & purification; Cervix Uteri / microbiology; Cervix Uteri / virology; Coinfection / microbiology; Coinfection / virology; Female; HIV Infections / virology; HIV-1 / physiology; Humans; Microbiota; Middle Aged; Mucus / microbiology; Mucus / virology; Vagina / microbiology; Vagina / virology; Vaginosis, Bacterial / microbiology; Young Adult
TL;DR:
Overall, it is found that HIV virions had significantly increased mobility in CVM from women with BV compared to CVMFrom women with Lactobacillus crispatus-dominant microbiota, regardless of whether symptoms were present.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: February 17, 2020
2020 review
Tuning Barrier Properties of Biological Hydrogels
[Review of ]. ACS APPLIED BIO MATERIALS, 3(5), 2875–2890.
author keywords: biological hydrogels; barriers; steric hindrance; adhesion; antibodies; agglutination; cross-linking; third-party modulators
TL;DR:
This review focuses on methods to tune the steric and adhesive barrier properties of biogels at the nanoscale, and the design requirements for developing effective third party modulators are reviewed.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: February 1, 2021
2019 journal article
Engineering Polymer-Binding Bispecific Antibodies for Enhanced Pretargeted Delivery of Nanoparticles to Mucus-Covered Epithelium
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 58(17), 5604–5608.
author keywords: antibodies; drug delivery; mucus; nanoparticles; PEGylation
MeSH headings : Antibodies, Bispecific / metabolism; Humans; Nanoparticles / metabolism; Polymers / metabolism
TL;DR:
This work explored a two-step "pretargeting" approach through engineering a bispecific antibody that binds both cell-surface ICAM-1 and polyethylene glycol (PEG) on the surface of nanoparticles, thereby effectively decoupling cell targeting from particle design and formulation.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: June 4, 2019
2019 journal article
Limited processivity of single motors improves overall transport flux of self-assembled motor-cargo complexes
PHYSICAL REVIEW E, 100(2).
MeSH headings : Biological Transport; Kinetics; Models, Biological; Molecular Motor Proteins / metabolism; Monte Carlo Method; Protein Binding
TL;DR:
It is found that lowering processivity, i.e., weaker binding of motors to MTs, can improve transport flux, shed light on the relationship between processivity and transport efficiency and offer a theory for the physiological benefits of low motor processivity.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: August 26, 2019
2019 journal article
Modeling Barrier Properties of Intestinal Mucus Reinforced with IgG and Secretory IgA against Motile Bacteria
ACS INFECTIOUS DISEASES, 5(9), 1570–1580.
author keywords: mucin; immunoglobulins; mucosal immunity; pathogen
MeSH headings : Agglutination; Animals; Bacteria / immunology; Bacteria / pathogenicity; Binding Sites; Humans; Immunoglobulin A, Secretory / chemistry; Immunoglobulin A, Secretory / metabolism; Immunoglobulin G / chemistry; Immunoglobulin G / metabolism; Intestinal Mucosa / immunology; Models, Theoretical; Mucins / chemistry; Mucins / immunology; Protein Binding
TL;DR:
A mathematical model is developed that improves the mechanistic understanding of Ab-enhanced barrier properties of mucus and highlights the ability for muco-trapping Ab to protect against motile pathogens at mucosal surfaces.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: October 7, 2019
2019 journal article
Overcoming anti-PEG antibody mediated accelerated blood clearance of PEGylated liposomes by pre-infusion with high molecular weight free PEG
JOURNAL OF CONTROLLED RELEASE, 311, 138–146.
author keywords: Polyethylene glycol antibodies; Anti-PEG antibodies; PEGylation; Polyethylene glycol; Anti-drug antibodies; Drug delivery; Accelerated blood clearance; Nanoparticles
MeSH headings : Administration, Intravenous; Animals; Antibiotics, Antineoplastic / administration & dosage; Antibiotics, Antineoplastic / pharmacokinetics; Antibodies / immunology; Doxorubicin / administration & dosage; Doxorubicin / pharmacokinetics; Female; Liposomes; Liver / metabolism; Mice, Inbred BALB C; Molecular Weight; Polyethylene Glycols / administration & dosage; Polyethylene Glycols / chemistry; Polyethylene Glycols / pharmacokinetics
TL;DR:
Surprisingly, it is found that 40 kDa free PEG effectively restored the prolonged circulation of PEGylated liposomes in the presence of high titers of pre-existing APA for at least 48 h in mice, and this results support further investigation of high molecular weight free P EG as a potential method to control and overcome high titer of APA.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: December 9, 2019
2019 journal article
Robust antigen-specific tuning of the nanoscale barrier properties of biogels using matrix-associating IgG and IgM antibodies
ACTA BIOMATERIALIA, 89, 95–103.
author keywords: Basement membrane; Extracellular matrix; Antibodies; Laminin; Particle tracking; PEG
MeSH headings : Animals; Antigens / chemistry; Collagen / chemistry; Drug Combinations; Hydrogels / chemistry; Immunoglobulin G / chemistry; Immunoglobulin M / chemistry; Laminin / chemistry; Membranes, Artificial; Nanoparticles / chemistry; Proteoglycans / chemistry
TL;DR:
A new approach is offered, based on weakly adhesive third-party molecular anchors, that allow for a variety of foreign entities to be trapped within a biogel simultaneously with exceptional potency and molecular specificity, without perturbing the bulk properties of the biogels.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: May 20, 2019
2014 journal article
Transient Antibody-Mucin Interactions Produce a Dynamic Molecular Shield against Viral Invasion
BIOPHYSICAL JOURNAL, 106(9), 2028–2036.
MeSH headings : Antibodies, Neutralizing / immunology; Antibodies, Neutralizing / metabolism; Antibodies, Viral / metabolism; Antibody Specificity; Cervix Uteri / virology; Female; HIV-1 / physiology; Humans; Immunoglobulin G / immunology; Kinetics; Mucins / metabolism; Mucus / virology; Protein Binding; Vagina / virology
TL;DR:
The model developed here is adaptable to other pathogens, mucosal barriers, and geometries, as well as kinetic and diffusional effects, providing a tool for hypothesis testing and producing quantitative insights into the dynamics of immune-mediated protection.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: August 6, 2018
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