In certain embodiments a lentiviral vector having optimized reduced size LCR with improved enhancer activity is provided. In certain embodiments direct treatment of a subject by direct introduction of the vector(s) described herein is contemplated. The lentiviral compositions may be formulated for delivery by any available route including, but not limited to parenteral (e.g., intravenous), intradermal, subcutaneous, oral (e.g., inhalation), transdermal (topical), transmucosal, rectal, and vaginal.

Provided is a polynucleotide the polynucleotide can be used as a WXRE transcriptional regulatory element used to increase the protein expression level of a protein expression system. A protein expression vector or a protein expression systems comprising the above-mentioned WXRE transcriptional regulatory element as well as the use thereof are also provided. The use of the WXRE transcriptional regulatory element can increase the expression level of a heterologous protein greatly with its biological activity unchanged.

The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

A composition formulated for intrathecal delivery of a recombinant adeno-associated virus (rAAV) vector comprising an AAVhu68 capsid carrying a human galactosylceramidase (GALC) gene for administration to Krabbe patients is provided. Also provided are novel gene sequences and uses thereof.

The present invention is based on the finding that the combination of a specific 5′UTR polynucleotide sequence (see SEQ ID NO 1) and the hCD33 secretory leader sequence in an expression cassette for expressing a polypeptide of interest results in a surprisingly better expression level of the polypeptide of interest compared to prior art expression cassettes. Based on this finding, the present invention inter alia provides novel expression cassettes, expression vectors and methods for producing a polypeptide of interest with high yield.

The present invention provides methods and compositions for labeling and/or targeting cells with increased calcium by providing a CREB reporter system. In addition, methods of treating disorders with activated cells such as brain disorders or cancer are also provided herein.

The present invention is directed to the cells, compositions and methods for the production of recombinant protein, wherein an f-met group on the 5′-terminus is enzymatically removed. In particular, the invention is directed to a production process for obtaining high levels of soluble recombinant CRM.sub.197 protein from E. coli. Cells preferably contain one or more mutations of disulfide reductase genes, so that disulfide reductase activity is reduced. The invention also relates to purification method for CRM.sub.197 as well as characterization of properly folded CRM.sub.197 protein.

The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

The present disclosure provides polynucleotide cassettes, expression vectors and methods for the expression of a gene in cone cells.

The present invention provides an integration-defective lentiviral vector based on a parental lentivirus and related methods, the integration-defective lentiviral vector including one or more of the following: (a) a mutation, deletion or other modification of one or more binding sites for a host factor involved in gene silencing; (b) an addition of one or more binding sites for a transcription activator, which can be natural (such as but not limited to ubiquitous and/or tissue/cell type specific) including but not limited to SP1 NFkB, or synthetic including but not limited to binding sites for tetracycline regulated trans activators tTA, rtTA, tT65, and/or rtT65; (c) one or more nucleic acid sequences from a SV40 genome, wherein the one or more sequences are obtained from a region of the SV40 genome upstream to the SV40 poly-adenylation signal; (d) a shRNA expression cassette, which encodes a shRNA directed to a host gene involved in epigenetic silencing and/or in DNA repair pathways; or (e) any combination of (a), (b), (c) and (d), wherein as compared to the parental lentivirus, the integration-defective lentiviral vector resists gene silencing.