The present invention provides expression vectors for cell-surface expression of polypeptides comprising a transmembrane domain of glycophorin A.

Angelman Syndrome (AS) is a genetic disorder occurring in approximately one in every 15,000 births. It is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. We have generated a Ube3a protein with additional sequences that should allow the secretion from cells and uptake by neighboring neuronal cells. This would confer a functional E6-AP protein into the neurons and rescue disease pathology.

The present invention relates to a novel composition of HIV-1 Env proteins that contain structurally and immunologically distinct VI/V2 domains. Methods of isolating such proteins, and methods of using such proteins as immunogens, therapeutic agents, vaccines, and test compounds for use in identifying a HIV antiviral are also provided.

The invention relates to a method for continuously producing and secreting recombinant Glucagon-like peptide-1 (GLP-1) by bacteria, more specifically E. coli. More specifically, the invention relates to use of novel bacterial expression vector for producing and enabling extracellular secretion of GLP-1, use of novel media composition for enhancing the secretion and enabling purification, and a perfusion-based fermentation system for continuous production and separation of recombinant GLP-1 peptide.

The present teachings provide methods for increasing protein secretion, e.g., chymosin in filamentous fungi by coexpressing certain chaperone(s) and/or foldase(s). The present teachings also provide filamentous fungi containing certain chaperone(s) and/or foldase(s) and a protein of interest for increased secretion.

The invention relates to pharmaceutical compositions comprising HLA fusion proteins for use in treating neoplastic disease. The invention also provides combination medicaments comprising both HLA fusion proteins and checkpoint inhibitors, for use in treating cancer.

The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. In more preferred embodiment the cytokine is G-CSF, erythropoietin or INF-2b.

The present invention provides materials and methods useful for error correction of nucleic acid molecules. In one embodiment of the invention, a first plurality of double-stranded nucleic acid molecules having a nucleotide mismatch are fragmented by exposure to a molecule having unidirectional mismatch endonuclease activity. The nucleic acid molecules are cut at the mismatch site or near the mismatch site, leaving a double-stranded nucleic acid molecule having a mismatch at the end or near end of the molecule. The nucleic acid molecule is then exposed to a molecule having unidirectional exonuclease activity to remove the mismatched nucleotide. The missing nucleotides can then be filled in by the action of, e.g., a molecule having DNA polymerase activity. The result is double-stranded nucleic acid molecules with a decreased frequency of nucleotide mismatches. Also provided are novel nucleic acid sequences encoding mismatch endonucleases, polypeptides encoded thereby, as well as nucleic acid constructs, transgenic cells, and various compositions thereof.

The invention provides a series of peptide signals which, when linked to a polypeptide of interest (POI), ensure that said polypeptide is secreted in high yields by a host cell such as Mycoplasma pneumoniae. The invention also provides fusion proteins tagged with said peptide signals, the nucleic acid sequences coding for them, host cells comprising said tagged fusion proteins and a variety of uses of the fusion proteins and the host cells.

Provided are isolated nucleic acids for expressing lysosomal polypeptides such as lysosomal acid -glucosidase (GAA) and vectors comprising the same. The invention provides an isolated nucleic acid encoding a chimeric polypeptide comprising a secretory signal sequence operably linked to a lysosomal polypeptide. The invention also provides an isolated nucleic acid comprising a coding region encoding a GAA and a GAA 3 untranslated region (UTR), wherein the GAA 3 UTR comprises a deletion therein. The invention further provides an isolated nucleic acid comprising a coding region encoding a GAA and a 3 UTR wherein the 3 UTR is less than about 200 nucleotides in length and comprises a segment that is heterologous to the GAA coding region. Also provided are methods of making and using delivery vectors encoding lysosomal polypeptides to produce the lysosomal polypeptide to treat subjects afflicted with a deficiency in the lysosomal polypeptide.