Abstract: The present invention is directed to recombinantly-modified adeno-associated virus (rAAV) having improved packaging efficiency, pharmaceutical compositions comprising such rAAV, and methods for their production and use. The present invention is particularly directed to recombinantly-modified adeno-associated virus (rAAV) that have been further modified to comprise Cis-Elements, including replication origins, promoters and enhancers, that are capable of regulating the replication of an rAAV genome and that improve rAAV replication. Preferably, such Cis-Elements are provided within domains of the rAAV that precede and/or follow the 5? and/or 3? inverted terminal repeated sequences (ITR) of an rAAV.

Abstract: The present invention is directed to non-naturally occurring peptides containing a membrane-penetrating amino acid sequence and further at least one polycationic moiety or peptide sequence. The peptides are suitable for use in delivery a cargo to the interior of a cell. Suitable cargo includes nucleic acid molecules (including DNA, RNA or PNA), polypeptides, or other biologically active molecules. The present invention is further directed to transfection complexes containing the non-naturally occurring peptides of the present invention in non-covalent association with at least one cationic lipid and a cargo to be delivered to the interior of a cell. The invention further relates to methods for the preparation and use of the non-naturally occurring peptides for the formation of transfection complexes and the delivery of a cargo to the interior of a cell in culture, an animal or a human. The invention also relates to compositions and kits useful for transfecting cells.

Abstract: The present disclosure in part provides compounds (i.e., PEG lipids) which are useful in pharmaceutical compositions, cosmetic compositions, and drug delivery systems, e.g, for use in lipid nanoparticle (LNP) formulations. The present disclosure also provides LNP formulations comprising PEG lipids described herein, and methods of using the same. For example, the LNPs provided herein are useful for the delivery of an agent (e.g, therapeutic agent) to a subject. The PEG lipids and LNPs provided herein, in certain embodiments, exhibit increased PEG shedding compared to existing PEG lipids and LNP formulations.

Abstract: Provided are methods for delivering lipid nanoparticles (LNPs) to a lung cell of a subject suffering from or at risk for primary ciliary dyskinesia (PCD), wherein the method comprises nebulizing a liquid pharmaceutical composition to generate an aerosolized pharmaceutical composition, and administering the aerosolized pharmaceutical composition to the subject.

Abstract: The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

Abstract: Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

Abstract: The present application provides materials and methods for treating a patient with one or more of Usher Syndrome Type 2A and ARRP, both ex vivo and in vivo; materials and methods for editing an USH2A gene containing a guanine deletion at nucleotide position c.2299. In addition, the present application provides one or more gRNAs or sgRNAs for editing an USH2A gene containing a guanine deletion at nucleotide position c.2299; a therapeutic comprising at least one or more gRNAs or sgRNAs for editing an USH2A gene containing a guanine deletion at nucleotide position c.2299; and a therapeutic for treating a patient with one or more of Usher Syndrome Type 2A and ARRP. The present application also provides a kit for treating a patient with one or more of Usher Syndrome Type 2A and ARRP.

Abstract: The invention relates to a method for the resolution of pro-tumour inflammation by means of a pharmaceutical preparation. Leukocytes are isolated from the buffy coat obtained from whole blood and a portion of the leukocytes is placed in a first pouch receiving a differentiation factor and stored in conditions that preserve cellular viability for several days, before a defined, fresh culture medium is supplied, after which said leukocyte portion is left to rest for a further several days, which results in the production of macrophages. A further portion of the leukocytes is placed in a second pouch and irradiated therein. The two pouches are then mixed and the supernatant is recovered to serve as pharmaceutical preparation. The invention also relates to the use in the treatment of cancers, either alone or in combination with other therapies, in human and veterinary medicine.

Abstract: Compositions are described for direct protein delivery into multiple cell types in the mammalian inner ear. The compositions are used to deliver protein(s) (such as gene editing factors) editing of genetic mutations associated with deafness or associated disorders thereof. The delivery of genome editing proteins for gene editing and correction of genetic mutations protect or restore hearing from genetic deafness. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

Abstract: Provided herein are compositions and methods for the design of synthetic regulatory sequences and for subsequent modulation of neural pathways.

Abstract: The disclosure provides methods of characterizing a sample of oligonucleotides of interest using liquid chromatography and mass spectrometry.

Abstract: Disclosed are a chimeric antigen receptor (CAR) targeting CLD18A2, and preparation method and use thereof. The extracellular binding region of the CAR comprises a protein specifically recognizing CLD18A2. The immune effector cell modified by the CAR can be used to treat tumors such as pancreatic cancer and stomach cancer.

Abstract: Disclosed are compositions and methods comprising one or more recombinant influenza viruses. Recombinant influenza viruses with mutated polymerases and/or rearranged genomes are disclosed. Constructs comprising different influenza nucleic acid sequences are also provided. Methods of inducing protecting immunity with the recombinant influenza viruses are disclosed. Also disclosed are methods of plasmid-free production of influenza virus comprising amplicons comprising one or more of influenza genes.

Abstract: The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A. In some embodiments, the present disclosure provides methods for dosing a hemophilia A patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor VIII polypeptide.

Abstract: Exosomes that express peptides in CD9 proteins, and smart exosomes that co-express two peptides incorporated into CD9 proteins to home delivery of the exosomes to a desired target and evade phagocytosis by macrophages, are described. Provided are exosomes useful for delivering drugs to desired targets. The exosomes comprise drugs, such as chemotherapeutic drugs, encapsulated in their core. The targets include pancreatic cancer cells.

Abstract: The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

Abstract: Disclosed are nucleic acid sequences comprising a modified HIV Gag sequence, wherein the modified HIV Gag sequence comprises, from 5? to 3?, a matrix domain (MA), capsid (CA) domain, SP1 region, nucleocapsid (NC) domain, SP2 region, and p6 domain, wherein the modified HIV Gag sequence further comprises an exogenous sequence of interest between the NC domain and the SP2 region. Disclosed are methods of producing a recombinant lentivirus comprising transfecting a cell with a plasmid comprising the nucleic acid sequence of one or more of the disclosed nucleic acid sequences in combination with an envelope plasmid. Disclosed are methods of monitoring lentivirus assembly, budding, and/or maturation comprising transfecting a cell with a plasmid comprising any one of the disclosed nucleic acid sequences in combination with an envelope plasmid, wherein the exogenous sequence of interest encodes a detection agent.

Abstract: Modified T-cells have paratopes against human TK1 epitopes, are made by producing monoclonal antibodies that are specific to TK1, creating chimeric antigen receptors (CARs) by fusion of the single-chain variable fragments (scFv) of the monoclonal antibodies to T-cell signalling domains, and transducing the CARs to the T-cells.

Abstract: Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

Abstract: Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.