The invention relates to the field of cell culture technology. It concerns the knockdown, using RNA interference, or gene knockout, of activating transcription factor 6 beta (ATF6B), or the combination of ceramide synthase 2 (CERS2) and TBC1 domain family member 20 (TBC1D20) proteins, which play central roles in the cellular secretion pathway. This downregulation leads to improved secretion of biopharmaceutically relevant products produced in mammalian cells. The invention specifically relates to mammalian cells having enhanced secretion of a recombinant therapeutic protein compared to a control cell, a method of producing said mammalian cell, a method for the production of a recombinant secreted therapeutic protein and the use of said mammalian cell for increasing the yield of a recombinant secreted therapeutic protein.

Methods and agents that target nanog or Oct4 expression or activity for treating or preventing cancer are disclosed. Alternative methods involve diagnosing cancer stage or type by identifying presence of cancer cells expressing nanog or Oct4. Also, disclosed are method of treating coronavirus infection that involves administering antiviral knockdown agents, such as oligonucleotide-based inhibitors.

A method for scarless genome editing is disclosed. In particular, the method provides scarless genome modification by using homology directed repair (HDR) steps to genetically modify cells and remove unwanted sequences. This method can be used for genome editing, including introducing mutations, deletions, or insertions at any position in the genome without leaving silent mutations, selection marker sequences, or other additional undesired sequences in the genome.

The present invention relates in part to the discovery of genes that are deregulated in cancer stem cells (e.g., melanoma stem cells). In some aspects, methods for treating individuals having melanoma are provided; the methods involve modulating (e.g., inducing, inhibiting, etc.) the activity of the cancer stem cell associated genes. In other aspects, cell surface genes that are upregulated in melanoma stem cells are targeted for the selective isolation, detection, and killing of cancer stem cells in melanoma. Other aspects of the invention relate to reagents, arrays, compositions, and kits that are useful for diagnosing and treating melanoma.

Among the various aspects of the present disclosure is the provision of methods and compositions for improving exercise endurance, performance, or tolerance using an S1P inhibiting agent.

Disclosed are means, methods and compositions of matter useful for treatment of lung inflammation associated with viral and bacterial infections, as well as with systemic inflammation, through administration of umbilical cord blood derived plasma-based compositions. In one embodiment the invention teaches administration of umbilical cord blood plasma together with pterostilbene, and/or sulforaphane, and/or thymoquinone, and/or Epigallocatechin gallate (EGCG) and/or n-acetylcysteine in an aerosolized manner to patients suffering from COVID-19 associated pulmonary deficiencies. In another embodiment, umbilical cord blood plasma is administered with immune stimulatory agents in order to concurrently inhibit propagation of viral load in the lung while suppressing pulmonary deficiencies.

This disclosure relates to the field of exosome delivery systems. In particular, compositions comprising adipose-derived exosomes that may be used as a delivery system are encompassed. The exosome delivery system can be used to deliver exogenous cargo such as miRNA and other inhibitory RNAs, as well as proteins, to target cells in a subject.

The present disclosure provides oligonucleotide compositions comprising (1) an oligonucleotide of the present disclosure, e.g., an ASO, siRNA, shRNA, DNA or RNA aptamer, gene therapy vector, miRNA, miRNA mimic, antimiR, DNA or RNA decoy, CpG oligonucleotide, or any therapeutic or diagnostic oligonucleotide known in the art, and (ii) a caprylic acid derivative, e.g., 5-CNAC. In some aspects, the oligonucleotide composition is formulated for delivery to the gastrointestinal tract. Thus, some aspects, the present disclosure provides oligonucleotide compositions for oral delivery comprising a therapeutic or diagnostic oligonucleotide (e.g., an ASO) and a caprylic acid derivative (e.g., 5-CNAC or de derivative thereof).

The disclosure provides for a targeting transfer RNA (ttRNA) that that suppresses nonsense mutations in messenger RNA, that comprises an anticodon sequence that binds to a stop codon and a variable loop sequence that comprises an RNA aptamer that has strong binding affinity to an RNA binding protein; and methods of use thereof.

Among the various aspects of the present disclosure is the provision of methods for treating pathologic calcification or bone formation and methods of inhibiting KIF26B that include administering a therapeutically effective amount of a synthetic nucleic acid against KIF26B. Compositions comprising a small hairpin RNA (shRNA) against KIF26B are also provided.