Abstract: Provided are methods of detecting replication competent virus, e.g., replication competent retrovirus such as gammaretrovirus or lentivirus, in a sample containing a cell transduced with a viral vector particle encoding a recombinant and/or heterologous molecule, e.g., heterologous gene product. The methods may include assessing transcription of one or more target genes, such as viral genes, that are expressed in a retrovirus but not expressed in the viral vector particle. Replication competent retrovirus may be determined to be present if the levels of RNA of the one or more target genes is higher than a reference value, which can be measured directly or indirectly, including from a positive control sample containing RNA from the respective target gene at a known level and/or at or above the limit of detection of the assay.

Abstract: In one aspect, bispecific proteins having the ability to specifically bind to both subdomain II of human HER2 and subdomain IV of human HER2 are provided. In another aspect, methods of treating a cancer or treating brain metastasis of a cancer using a bispecific protein that specifically binds to subdomain II and subdomain IV of human HER2 are provided.

Abstract: This disclosure relates to methods and compositions for treating cancer by administering opioid growth factor receptor (OGFR) antagonists. In particular, the present disclosure relates to methods of administering OGFR antagonists locally to the site of cancer cells in the patient diagnosed with cancer.

Abstract: The present invention provides gene edited modified immune cells suitable for adoptive T cell therapy comprising a nucleic acid capable of downregulating CD3?, CD3?, CD3?, B2M, CIITA, TAP1, TAP2, TAPBP, NLRC5, HLA-DM, RFX5, RFXANK, RFXAP, and invariant chain; and further comprising an exogenous nucleic acid encoding a chimeric antigen receptor (CAR), an engineered T cell receptor (TCR), a Killer cell immunoglobulin-like receptor (KIR), dominant negative receptor and/or a switch receptor. Also provided are compositions and methods for generating the modified immune cell, and methods of using the modified immune cells for adoptive therapy and treating a disease or condition.

Abstract: The present disclosure discusses system and methods for improving the efficiency of a remote computing device. The system and methods include generate a profile and delivery schedule for the remote computing device. The system can dynamically update the delivery schedule of future requests the system transmits to the remote computing device based on responses to current request.

Abstract: The present disclosure relates in some aspects to methods, cells, and compositions for preparing cells and compositions for genetic engineering and cell therapy. Provided in some embodiments are streamlined cell preparation methods, e.g., for isolation, processing, incubation, and genetic engineering of cells and populations of cells. Also provided are cells and compositions produced by the methods and methods of their use. The cells can include immune cells, such as T cells, and generally include a plurality of isolated T cell populations or types. In some aspects, the methods are capable of preparing of a plurality of different cell populations for adoptive therapy using fewer steps and/or resources and/or reduced handling compared with other methods.

Abstract: Provided in some aspects are compositions of cells for treating subjects with disease and conditions such as non-Hodgkin's lymphoma (NHL), and related methods, compositions, uses and articles of manufacture. In some embodiments, the disease or condition is a B-cell non-Hodgkin lymphoma (B-cell NHL). The cells generally express recombinant receptors such as chimeric antigen receptors (CARs) for targeting an antigen, such as CD 19, on cells of the lymphoma.

Abstract: New treatments for Ikaros and/or Aiolos mediated disorders are provided that comprise administering an effective amount of a cereblon binder that degrades Ikaros or Aiolos by the ubiquitin proteasome pathway.

Abstract: The present invention relates to interleukin-2 fusion proteins. More specifically, the invention provides, in part, fusion proteins that include a interleukin-2 protein moiety joined to a Bcl-2 family member protein moiety.

Abstract: The present invention provides compounds, compositions thereof, and methods of using the same.

Abstract: Formulated and/or co-formulated liposomes comprising TLR prodrugs and/or TLR Lipid Moieties and methods of making the liposomes are disclosed herein. The TLR prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit Toll-Like Receptor (e.g., TLR1/2, TLR4, and/or TLR7). The TLR prodrugs can be formulated and/or co-formulated into a liposome to provide a method of treating cancer, immunological disorders, and other disease by utilizing a targeted drug delivery vehicle.

Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Abstract: The present disclosure provides industrially scalable methods of making (Z)-endoxifen or a salt thereof, crystalline forms of endoxifin, and compositions comprising them. The present disclosure also provides methods for treating hormone-dependent breast and hormone-dependent reproductive tract disorders.

Abstract: Disclosed herein are compounds and methods of using such compounds for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging, or for modulating one or more energy biomarkers, normalizing one or more energy biomarkers, or enhancing one or more energy biomarkers, wherein the compounds are tocopherol quinone derivatives. Further disclosed are compounds, compositions, and methods for treatment of, or prophylaxis against, radiation exposure.

Abstract: Disclosed herein are circular RNAs and transfer vehicles, along with related compositions and methods of treatment. The circular RNAs can comprise group I intron fragments, spacers, an IRES, duplex forming regions, and/or an expression sequence, thereby having the features of improved expression, functional stability, low immunogenicity, ease of manufacturing, and/or extended half-life compared to linear RNA. Pharmaceutical compositions comprising such circular RNAs and transfer vehicles are particularly suitable for efficient protein expression in immune cells in vivo. Also disclosed are precursor RNAs and materials useful in producing the precursor or circular RNAs, which have improved circularization efficiency and/or are compatible with effective circular RNA purification methods.

Abstract: Disclosed herein are compositions and methods for topical delivery of mTOR inhibitors. In one embodiment, an anhydrous composition includes one or more mTOR inhibitors, one or more solvents, one or more gelling agents, and one or more antioxidants. Also disclosed herein are methods to treat skin disorders using such compositions.

Abstract: A proprotein containing a functional protein coupled to a peptide mask that inhibits binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask.

Abstract: Compositions and methods for multiplex delivery and gene editing in vitro are provided.

Abstract: Disclosed are methods and systems for producing polymer-DNA nanoparticles of a predetermined size. In one example, a method includes mixing together a first solution comprising deoxyribonucleic acid (DNA) with a second solution comprising a cationic polymer to obtain a polyplex solution, and at a predetermined time subsequent to mixing together the first solution and the second solution, adding a polyplex stabilizing agent to stabilize the size of the polyplex. In this way, transfection efficacy of the polymer-DNA nanoparticles may be improved, in particular with reference to transfection of suspension cells for production of viral vectors.

Abstract: The present disclosure provides activatable masked antigen binding proteins comprising an antigen binding protein attached to universal masking moieties by peptide linkers. The universal masking moieties dimerize with each other to form a dimerized masking complex that blocks binding between the antigen binding domain and its target antigen. The individual masking moieties and the dimerized masking complex do not bind specifically to the antigen binding domain. The masking moieties form stable dimers because their association with each other mimics homodimers or heterodimers found in naturally-occurring immunoglobulin or cell receptor molecules. The dimerization of the masking moieties does not involve covalent bonding and can be optimized by engineering interchain association through structure complementarity such as knob-in-hole.