The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

The invention relates to multimers such as tetramers of polypeptides and tetramers and octamers of effector domains, such as antigen binding sites (eg, antibody or TCR binding sites that specifically bind to antigen or pMHC, or variable domains thereof) or peptides such as incretin, insulin or hormone peptides.

The invention pertains to a method to identify an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein, wherein the combination is effective when the transmembrane E3 ubiquitin ligase is capable of decreasing the surface level of the membrane-bound protein upon forced dimerization, preferably by ubiquitination of the membrane-bound protein. The method of the invention comprises a step of exposing a cell to a heterobifunctional molecule, wherein the heterobifunctional molecule comprises a first binding domain capable of specific binding to an extracellular portion of the transmembrane E3 ubiquitin ligase, and a second binding domain capable of specific binding to an extracellular portion of the membrane-bound protein. The method further comprises a step of determining the decrease in surface level of the membrane-bound protein. The invention additionally pertains to a heterobifunctional molecule targeting an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein.

This application provides the first observation of methylmalonylation/malonylation in organic acidemias (OAs), such as methylmalonic acidemia (MMA) and propionic acidemia (PA), which results in modification of enzymes in key pathways dysregulated in OAs, including sirtuin 5 (SIRT5). Hyperacylation of SIRT5 prevents it from de-acylating CPS1 (including removing methymalonyllation), which prevents activation of CPS1 and likewise, inhibits a key component of the glycine cleavage system, GCSH. Based on these observations, provided herein is a mutant form of SIRT5 containing four mutated lysines that cannot accept acyl groups, methods of its use for treating OA patients, and kits.

Recombinant Fibrinogen C Domain Containing 1 (rFibcd1) proteins and methods for using the same in the treatment of muscle atrophy are provided as are vectors, host cells, pharmaceutical compositions and modified RNA molecules encoding the rFibcd1 proteins.

Modified microorganisms, pharmaceutical compositions thereof, and methods of preventing and treating the coronavirus disease 2019 (COVID-19) are disclosed.

Compositions and methods for treating a viral infection may comprise use of a viral recognition-site inhibiting agent composition. A viral recognition-site inhibiting agent composition of the present disclosure may substantially inhibit, reduce, or block virus bind to the LDLRAD3 host receptor and reduces the infectivity of a virus for a host cell. A method of treating a viral infection may comprise administering a composition comprising a viral recognition-site inhibiting agent of the present disclosure, to a subject and reducing the infectivity of the virus for a host cell of the subject. The compositions may be administered via intranasal or systemic administration to treat or prevent a viral infection, for example an alphavirus infection.

Methods for the rapid elimination of carbon monoxide (CO) from CO-bound hemoglobin, myoglobin and cytochrome c oxidase in subjects with CO poisoning are described. The disclosed therapy involves the use of rationally designed, modified, regulator of CO metabolism (RcoM) proteins and pharmaceutical compositions thereof, which scavenge carbon monoxide from poisoned tissue. The recombinant RcoM compositions are infused into blood, where they rapidly sequester carbon monoxide and limit the toxic effects of carbon monoxide on cellular respiration, oxygen transport and oxygen utilization.

Engineered trimeric CD70 proteins for use in ex vivo T cell manufacturing are described. Use of the proteins during manufacturing creates expanded T cell populations with enhanced properties such as earlier proliferation in culture; selective expansion of nave and memory T cell subsets; longer persistence in vivo following administration to a subject; and improved therapeutic effect. Use of the proteins as therapeutics provide anti-cancer and anti-viral effects. The proteins can also be used as agonistic cell culture reagents in in vitro uses.

Provided herein are mammalian cells comprising a first exogenous nucleic acid encoding a DNAse protein and a second exogenous nucleic acid encoding another DNAse protein, such as DNASE1 protein and DNASE1L3 protein, that have improved properties, including the ability to degrades extracellular chromatin and remove Neutrophil Extracellular Traps (NETs). Use of these cells, including the use in the treatment of a subject in need thereof, is also contemplated.