The present invention provides HIV-derived lentivectors which are safe, highly efficient, and very potent for expressing transgenes for human gene therapy, especially, in human hematopoietic progenitor cells as well as in all other blood cell derivatives. The lentiviral vectors comprise promoters active to promote expression specific to cell types or tissues. Further, promoters are providing that are amenable to control by activators, enhancers, or repressors. These vectors are in a self-inactivating configuration for biosaftey. Additional promoters are also described. The vectors can also comprise additional transcription enhancing elements such as the wood chuck hepatitis virus post-transcriptional regulatory element, without any decrease in the specificity or control exerted by the promoters. These vectors therefore provide useful tools for genetic treatments such as inherited and acquired lympho-hematological disorders, gene-therapies for cancers especially the hematological cancers, as well as for the study of hematopoiesis via lentivector-mediated modification of human HSCs.

Methods of modulating expression of a target nucleic acid in a cell are provided including use of multiple orthogonal Cas9 proteins to simultaneously and independently regulate corresponding genes or simultaneously and independently edit corresponding genes.

An objective of the present invention is to provide an improved negative-strand RNA viral vector and a use thereof, the negative-strand RNA viral vector exhibiting transient high expression of genes loaded in the vector and enabling the rapid removal of the vector after said expression. It was discovered that by adding a micro-RNA target sequence to the NP, P, or L gene of a negative-strand RNA viral vector, it is possible to control the expression of the vector depending on the micro-RNA expressed by the introduction cell. In particular, when a micro-RNA target sequence was added to the NP or P gene, the expression of the vector decreased depending on the micro-RNA, and the removal of the vector was promoted, while the effect was reversed when a micro-RNA target sequence was added to the L gene. The vector can be applied in cell therapy and regenerative medicine and can be used as a therapeutic vector that targets cancer.

The present invention relates to a process for producing and selecting for targeted mutations in bacterial genomes. In particular, the process relates to the transformation of bacteria with a Recombination Element which comprises the desired mutation followed by homologous recombination of the Recombination Element into the bacterial genome; the CRISPR/Cas system is then used to eliminate bacteria which do not have the desired mutation.

The present invention provides constructs comprising modified riboswitches to regulate expression of a transgene within a subject. Methods of treating a disease, specifically an eye disease, are also contemplated.

The present invention relates generally to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the present invention provides novel synthetic genes and genetic constructs which are capable of repressing delaying or otherwise reducing the expression of an endogenous gene or a target gene in an organism when introduced thereto.

CHO cell-specific synthetic promoter constructs for expressing recombinant proteins, a library of promoter constructs thereof, and a method for producing the promoter constructs. The promoter constructs enable precise control of recombinant gene transcription over three orders of magnitude, with the top expressing promoters capable of double the transcriptional activity of the CMV promoter.

Compositions and methods are provided for Tat-inducible expression of a CRISPR-associated endonuclease by a truncated HIV LTR promoter containing at least a core region and a TAR region of a HIV LTR promoter. The compositions may be used as a therapeutic treatment for the treatment and/or prevention of HIV.

An epigenetic silencer factor (ESP), or polynucleotide encoding therefor, for use in the treatment of cancer, wherein the ESF comprises a transcription factor DNA-binding domain operably linked to at least one epigenetic effector domain, wherein the transcription factor is an oncogenic transcription factor or a cancer-associated transcription factor, wherein the cancer is selected from the group consisting of: glioma, gliobastoma, medulloblastoma, astrocytoma, neuroblastomas, ependymoma, meningioma, retinoblastoma, rhabdomyosarcoma, lung cancer, prostate cancer, breast cancer, liver cancer, pancreatic cancer (e.g. human pancreatic ductal adenocarcinoma), bladder cancer, oropharyngeal cancer, kidney cancer, colon cancer (e.g. colon adenocarcinoma), colon-rectal cancer (CRC), or a metastasis of any of the foregoing.

The invention relates to polypeptides having peroxygenase activity and compositions comprising such polypeptides. The invention also relates to improved methods of producing such polypeptides in yeasts.