Abstract: Methods of modeling the in vivo efficacy of drug combinations for the treatment or prevention of viral infection are described. The described methods combine data for single drugs and drug combinations from pharmacokinetic, pharmacodynamic, and viral dynamics models under a series of estimated in vivo drug potencies to provide predictions of the in vivo effects of the drug combinations. These predictions can be used to more accurately select drugs and drug treatment regimens that can be successful in controlling viral infection in animal studies, clinical trials and in medical or veterinary interventions. Also described is a method of treating or preventing filovirus infections using combinations of orally available drugs based on predictions from the modeling methods.

Abstract: Provided are methods, kits and compositions related to toxicity associated with administration of cell therapy for the treatment of diseases or conditions, e.g., cancer, including methods for use in predicting and treating a toxicity. In some embodiments, the toxicity is a neurotoxicity or cytokine release syndrome (CRS), such as a severe neurotoxicity or a severe CRS. The methods generally involve detecting a parameter of a biomarker or individually a parameter of each biomarker in a panel of biomarkers, such as a concentration, amount or activity, and comparing the detected parameter to a reference value for the parameter to determine if the subject is at risk for developing the toxicity, such as neurotoxicity or CRS or severe neurotoxicity or severe CRS.

Abstract: Provided herein are kits and methods for detecting, monitoring, and classifying a nongonococcal urethritis (NGU) infection in a male subject based on a genitourinary microbiome of a subject, as well as related methods of treating. Also provided are kits and methods for classifying a risk of human immunodeficiency virus (HIV) infection in a subject based on a genitourinary microbiome of a subject, as well as related methods of preventing infection.

Abstract: Provided are methods, kits and compositions related to toxicity associated with administration of cell therapy for the treatment of diseases or conditions, e.g., cancer, including methods for use in predicting and treating a toxicity. In some embodiments, the toxicity is a neurotoxicity or cytokine release syndrome (CRS), such as a severe neurotoxicity or a severe CRS. The methods generally involve detecting a parameter of a biomarker or individually a parameter of each biomarker in a panel of biomarkers, such as a concentration, amount or activity, and comparing the detected parameter to a reference value for the parameter to determine if the subject is at risk for developing the toxicity, such as neurotoxicity or CRS or severe neurotoxicity or severe CRS.

Abstract: The current disclosure relates to methods and compositions for increasing functional expression of BRD9 in a cell. The methods and compositions can be incorporated into methods for treating cancer through the administration of BRD9 activating therapies. Accordingly, aspects of the disclosure relate to compositions and methods for treating cancer, a pre-malignant disease, or a dysplastic disease in a subject. The method can comprise administering a BRD9 activating therapy to the subject.

Abstract: Embodiments of the present disclosure are directed to methods and compositions for inhibiting cytomegalovirus (CMV) in a transplant recipient. In some embodiments, the methods are directed to inhibiting CMV reactivation in a transplant recipient with a CMV-seropositive serological status, the method comprising administering an effective amount of a compound to block IL-6 function. In some embodiments, the methods are directed to preventing CMV infection in a transplant recipient, wherein a transplant donor has a CMV-seropositive serological status, the method comprising administering an effective amount of a compound to block IL-6 function. In still other embodiments, a composition comprising a compound to block IL-6 function is administered to a transplant recipient with a CMV-seropositive serological status to prevent CMV reactivation.

Abstract: The present disclosure describes an immunotherapy delivery hydrogel system. The immunotherapy delivery hydrogel system can be degradable and can release therapeutic agents at a tunable rate, and in a controlled manner. The immunotherapy delivery hydrogel system includes a hydrogel matrix and cancer therapeutic agent(s) associated with the hydrogel matrix. The hydrogel system can further include tumor cell-attractant(s) conjugated to the hydrogel matrix. The tumor cell-attractant(s) and the cancer therapeutic agent(s) act synergistically to treat cancer.

Abstract: Provided herein are compositions and methods comprising mutated coronavirus “S” spike proteins or receptor binding domains thereof that have an increased expression level, yield and stability compared to its corresponding native or wild-type coronavirus spike protein under the same expression, culture or storage conditions. These mutated spike proteins can be used for generating a protein-based vaccine against one or more coronaviruses.

Abstract: Mutated and/or truncated malarial circumsporozoite proteins (CSP) and associated nucleic acids that are more stable and highly expressed in mammalian cells are described. The mutated and/or truncated CSP and associated nucleic acids can be expressed to produce malaria vaccine antigens.

Abstract: The disclosure provides methods for inducing Notch signaling in a targeted manner within aggregations of cells. The methods include contacting the aggregation of cells with a bi-specific molecule that facilitates trans-binding of Notch receptor. The bi-specific molecule comprising a cell-targeting domain that specifically binds to a cell-specific antigen expressed in the aggregation of cells, and a Notch-binding domain that specifically binds to Notch receptor. In some aspects, the disclosed methods and reagents provide methods of promoting pro-inflammatory states in tumor micro-environments.

Abstract: The disclosure provides methods and compositions for microlumen targeting in the treatment of cancers characterized by solid tumors or cell clusters, such as circulating tumor cell (CTC) clusters and disseminated tumor cell (DTC) clusters. The methods and compositions specifically target epigen in microlumenal space between two or more cancer cells and reduce the expression, functionality and/or concentration of epigen within the microlumenal space. The methods and compositions can be part of methods of treating cancer in a subject wherein the cancer is characterized by a solid tumor, a circulating tumor cell (CTC) cluster, and/or a disseminated tumor cell (DTC) cluster. The reduced levels of functional epigen in the microlumen result in reduced incidence of metastasis and increased susceptibility of the tumor cells to additional therapeutic interventions.

Abstract: The present disclosure provides, among other things, helper-dependent adenoviral serotype 35 (Ad35) vectors. In various embodiments, helper-dependent Ad35 vectors can be used to deliver a therapeutic payload to a subject in need thereof. Exemplary payloads can encode replacement proteins, antibodies, CARs, TCRs, small RNAs, and genome editing systems. In certain embodiments, a helper-dependent Ad35 vector is engineered for integration of a payload into a host cell genome. The present disclosure further includes methods of gene therapy that include administration of a helper-dependent Ad35 vector to a subject in need thereof.

Abstract: Methods and compositions for treatment of prostate cancers, such as androgen receptor (AR) deficient and androgen receptor (AR) low cancers, are disclosed. The methods include administration of an agent that inhibits activity of eIF4F or an agent that disrupts the eIF4F translation-initiation complex (composed of eIF4E, eIF4A, and eIF4G).

Abstract: A method for detecting the binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in a cell, including: contacting a permeabilized cell or nucleus with a specific binding agent that specifically recognizes the chromatin-associated factor of interest, wherein the specific binding agent is linked to a nuclease that is inactive or an activatable transposome; activating the nuclease or transposase, thereby excising the sequence of chromatin DNA bound to the chromatin-associated factor of interest; isolating the excised DNA; and determining the sequence of the excised DNA, thereby detecting binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in the cell.

Abstract: A method for detecting the binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in a cell, including: contacting a permeabilized cell or nucleus with a specific binding agent that specifically recognizes the chromatin-associated factor of interest, wherein the specific binding agent is linked to a nuclease that is inactive or an activatable transposome; activating the nuclease or transposase, thereby excising the sequence of chromatin DNA bound to the chromatin-associated factor of interest; isolating the excised DNA; and determining the sequence of the excised DNA, thereby detecting binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in the cell.

Abstract: Hematopoeitic stem/progenitor cells (HSPC) and/or non-T effector cells are modified to express an extracellular component including a tag cassette. The tag cassette can be used to activate, promote proliferation of, detect, enrich, isolate, track, deplete and/or eliminate modified cells. The cells can also be modified to express a binding domain.

Abstract: Siderocalin-metal chelator combinations that bind metallic radioisotopes used in nuclear medicine with high affinity are described. The high affinity siderocalin-metal chelator combinations include a number of chelator backbone arrangements with functional groups that coordinate with metals. The siderocalin-metal chelator combinations can be used to deliver radionuclides for imaging and therapeutic purposes.

Abstract: Devices and methods for bio-specimen refrigeration are provided. In an embodiment, the bio-specimen refrigeration devices of the present disclosure include a housing having a lid and a base portion, wherein the lid is selectively moveable between an open position and a closed position; a coolant cartridge chamber disposed in the housing and configured to fluidically couple with a coolant cartridge disposed in the coolant cartridge chamber; and a cooling chamber disposed in the housing and configured to receive a fluid coolant from the coolant cartridge, wherein in the closed position, the lid seals the cooling chamber.

Abstract: The current disclosure provides protein residue mapping using a combination of deep mutational scanning and phage display high throughput sequencing. The disclosed methods allow mapping of antibody epitopes and determination of changes in residues of a protein that abolish binding of the protein to a candidate binding molecule.

Abstract: Methods and compositions for treatment of malignancies are provided. The methods utilize implantation of engineered, programmable hydrogel depots capable of long-term molecule release into close proximity of the tumor. By providing gradients of immune cell chemokines and releasing immune checkpoint inhibitors, the hydrogel implants are effective at elimination of tumor cells via immune cell-mediated cell death.