Abstract: The present disclosure provides compositions for viral gene therapy, e.g. Adeno-Associated virus-directed gene therapy, and methods of using the same for the treatment and/or prevention of cholesterol storage diseases or disorders, such as Niemann-Pick disease, Type C.

Abstract: Disclosed herein are novel methods of treating substance use disorders, mitigating the development of substance addiction, reducing the severity of substance withdrawal symptoms, or reducing or preventing substance relapse by providing to the patient a therapeutically effective amount of a Medication Assisted Treatment agent and a selective dopamine D3 receptor antagonist/partial agonist. In addition, the D3 antagonists/partial agonists described herein may be used to augment the effectiveness of current Medication Assisted Treatment regimens (e.g. methadone or buprenorphine) for the treatment of substance use disorders, including opioid use disorders.

Abstract: Disclosed herein novel dopamine D3 receptor selective antagonists/partial agonists compounds with high affinity and metabolic stability useful for the treatment of psychiatric and neurological disorders and as research and diagnostic tools. Also disclosed are methods of making the compounds.

Abstract: Embodiments of recombinant HIV-1 gp120 proteins that contain a V1 deletion are disclosed. Also provided are gp140, gp145, and gp160 proteins containing the V1 deletion, as well as HIV-1 Env ectodomain trimers containing protomers containing the V1 deletion. Nucleic acid molecules encoding these proteins are also provided. In several embodiments, the disclosed recombinant HIV-1 proteins and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

Abstract: A compound of Formula I or a pharmaceutically acceptable ester, amide, solvate, or salt thereof, or a salt of such an ester or amide or a solvate of such an ester amide or salt: wherein the definitions of R1-R13 and L1-L4 are provided in the disclosure, and wherein R14 is a group capable of binding to prostate-specific membrane antigen (PSMA).

Abstract: Methods for producing synthetic single-domain monoclonal antibody libraries using humanized llama nanobody framework sequences, libraries obtainable by the method, as well as antibodies selected from the libraries are described. In particular, synthetic single-domain monoclonal antibodies that specifically bind to the spike protein of SARS-COV-2 and neutralize SARS-COV-2 infection are described. Use of the disclosed antibodies for the detection, prophylaxis and treatment of SARS-COV-2 infection is described.

Abstract: Disclosed are nucleic acids and polypeptides which provide the co-expression of interleukin (IL)-21 and IL-15 by a host cell, each interleukin being bound to the cell membrane by a cell membrane anchor moiety. Also disclosed are related recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

Abstract: Anti-EBV gH antibodies, anti-EBV gL antibodies, anti-EBV gH/gL antibodies, and compositions of matter useful for the detection, diagnosis, prevention, and treatment of Epstein Barr Virus infection in humans, and methods of using those compositions of matter for the same.

Abstract: Disclosed herein are methods for systemically editing a gene in a subject and for systemically treating a genetic condition in a subject using a dual-vector CRISPR-Cas therapy. The methods comprise administering to the subject, via systemic administration, a gene editing AAV vector encoding a CRISPR effector protein (e.g., a Cas protein) and a targeting AAV vector providing one or more gRNAs targeted to the gene. In the methods, the ratio of the targeting AAV vector to the gene editing vector is greater than or equal to 2. Also provided are dual-vector systems for editing a gene or treating a genetic disease in a subject.

Abstract: The invention relates to treatments for fibrosis by administering a neutrophil elastase inhibitor, such as alvelestat. In particular, the invention relates to treatments for fibrosis in combination with another disease, such as organ rejection, for example bronchiolitis obliterans syndrome optionally associated with graft-versus-host-disease.

Abstract: Disclosed are methods of preparing an isolated population of human papillomavirus (HPV)-specific T cells comprise dividing an HPV-positive tumor sample into multiple fragments; separately culturing the multiple fragments; obtaining T cells from the cultured multiple fragments; testing the T cells for specific autologous HPV-positive tumor recognition; selecting the T cells that exhibit specific autologous HPV-positive tumor recognition; and expanding the number of selected T cells to produce a population of HPV-specific T cells for adoptive cell therapy. Related methods of treating or preventing cancer using the T cells are also disclosed.

Abstract: The disclosure of a compound of Formula I or a pharmaceutically acceptable salt thereof The variables W, R1, R2, R3, and R4 are defined in the disclosure. The disclosure provides a compound or salt of Formula I together with a pharmaceutically acceptable carrier. The disclosure also provides methods of treating a patient for Parkinson's disease and related syndromes, dyskinesia, especially dyskinesias secondary to treating Parkinson's disease with L-DOPA, neurodegenerative disorders such as Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, or substance use disorders, the methods comprising administering a compound of Formula I or salt thereof to the patient. The disclosure provides combination methods of treatment in which the compound of Formula I is administered to the patient together with one or more additional active agents.

Abstract: HIV-1 Env ectodomain trimers stabilized in a prefusion mature closed conformation and methods of their use and production are disclosed. In several embodiments, the HIV-1 Env ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject. In additional embodiments, the therapeutically effective amount of the HIV-1 Env ectodomain trimers can be administered to a subject in a method of treating or preventing HIV-1 infection.

Abstract: Disclosed herein are methods for detecting presence of a target nucleic acid (such as an influenza virus nucleic acid) in a sample. In some embodiments, the methods include contacting the sample with a first probe capable of hybridizing to the target nucleic acid and a second probe capable of hybridizing to the target nucleic acid, contacting the resulting complex with one or more gap filling reagents, thereby producing a gap-filled target nucleic acid, isolating and amplifying the gap-filled target nucleic acid. The amplified gap-filled target nucleic acid covalently linked to the substrate is then detected, for example with a detectably labeled probe. Also disclosed herein are probes capable of hybridizing to influenza virus nucleic acids. The disclosure also includes kits for detecting and/or discriminating influenza virus nucleic acids in a sample. In some examples, the kits include two or more of the disclosed probes.

Abstract: Gingerenone A prodrug compounds have a structure according to Formula I, or a pharmaceutically acceptable salt thereof wherein one of R1 and R2 is H or —C(O)—R and the other of R1 and R2 is —C(O)—R. Each R independently is RA or where RA is C18-C22 alkenyl, and RB is an amino acid side chain. The compounds are useful for inhibiting or eliminating senescence, reducing a level of interleukin-2 (IL-2), reducing a level of interleukin-5 (IL-5), increasing a level of a metabolite that exerts an antioxidant effect, increasing a level of an RA-containing lipid, or any combination thereof. The compounds may be administered to a subject having a senescence-associated disease or disorder, neuroinflammation, pain, an amino acid deficiency, atopy, itch, or any combination thereof.

Abstract: The disclosure provides various embodiments of catheters having articulable ends that can be used for various procedures. Embodiments of methods are also provided that can be performed with catheters in accordance with the present disclosure.

Abstract: Monoclonal antibodies that specifically bind glypican-1 (GPC1) are described. Chimeric antigen receptor (CAR) T cells, immunotoxins and other antibody conjugates based on the GPC1-specific antibodies are also described. The disclosed CAR T cells, immunotoxins, GPC1-specific antibodies and conjugates thereof can be used, for example, in the diagnosis or treatment of GPC1-positive pancreatic cancer and other cancers.

Abstract: The present disclosure provides compositions for viral gene therapy, e.g. Adeno-Associated virus-directed gene therapy, and methods of using the same for the treatment and/or prevention of cholesterol storage diseases or disorders, such as Niemann-Pick disease, Type C.

Abstract: Administration of aquaporin-1 (AQP1) complementary deoxyribonucleic acid (cDNA) to a salivary gland prior to treatment with ionizing radiation (IR) prevents the subsequent IR-induced loss in function. The administration of AQPI (e.g., human AQP1: hAQP1) prior to IR treatment (e.g., in patients with head and neck cancer) can reduce or prevent IR-induced salivary hypofunction, resulting in an elevated salivary output.

Abstract: Respiratory syncytial virus (RSV) infection may lead to severe respiratory illness in young children. Thus, there is a need for a live attenuated vaccine, which would mimic the natural course of infection without causing illness; however, restricting viral replication also reduces the immune response. Reported herein is a method of vaccination using a single dose of a recombinant RSV lacking the M2-2 protein that surprisingly induced a stronger immune response to RSV than previous vaccine candidates despite being more restricted in replication.