Methods and compositions for producing heme and treating sideroblastic anemia are disclosed.

In certain embodiments a lentiviral vector for the treatment of Wiskott-Aldrich Syndrome (WAS) is provided. In certain embodiments the vector comprises an expression cassette comprising a nucleic acid construct comprising an effective fragment of the endogenous promoter of the WAS gene where said promoter has maximum length of 600 bp and contains the sequence of HS1pro, and a nucleic acid that encodes the Wiskott-Aldrich Syndrome protein (WASp) operably linked to the effective fragment of the endogenous promoter of the WAS gene.

Non-human animal cells and non-human animals comprising CRISPR/Cas synergistic activation mediator system components and methods of making and using such non-human animal cells and non-human animals are provided. Methods are provided for using such non-human animals to increase expression of target genes in vivo and to assess CRISPR/Cas synergistic activation mediator systems for the ability to increase expression of target genes in vivo.

The present invention relates to the field of recombinant viral vectors suitable for the delivery of therapeutic genes in vivo. Described is an adeno-associated virus (AAV) vector comprising (i) a human growth hormone intron 3 (hGHi3) sequence (ii) a synapsin promoter sequence and/or (iii) a progranulin 3′ untranslated region (UTR) sequence, operably coupled to a polynucleotide sequence encoding a polypeptide of interest. Specific use of such a vector lies in the enhanced expression of a polypeptide of interest, such as progranulin (PGRN), to treat subjects who have a genetic mutation or intrinsic polypeptide level that is below a physiologically normal level.

Provided are recombinant nucleic acids (e.g., vectors), and related methods, for expression of a target gene in a host cell. The recombinant nucleic acids comprise a promoter comprising a nucleic acid sequence having at least 70% sequence identity to a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9; a cloning site for insertion of a nucleic acid encoding the target gene; and at least one non-promoter regulatory element required for the expression of the target gene in the host cell.

The object of the present invention is to provide a polynucleotide which can be inserted into an expression vector and can enhance the transcriptional activity of a predetermined promoter under heart failure.

The object is achieved by an enhancer polynucleotide comprising a polynucleotide consisting of a sequence having 80% or more identity with a sequence represented by SEQ ID NO: 1, or a polynucleotide consisting of a sequence having 80% or more identity with a sequence represented by SEQ ID NO: 2, wherein the enhancer polynucleotide responds to heart failure (where the enhancer polynucleotide excludes a polynucleotide having the same sequence as a sequence represented by SEQ ID NO: 13 and a polynucleotide having the same sequence as a sequence represented by SEQ ID NO: 12).

In certain embodiments a lentiviral vector for the treatment of X-linked chronic granulomatous disease (X-CGD) is provided. In certain embodiments the vector comprises an expression cassette comprising a nucleic acid construct comprising a CYBB promoter or effective fragment thereof; and a nucleic acid that encodes gp91.sup.phox operably linked to the CYBB promoter or promoter fragment.

Provided herein are polynucleotide constructs comprising a CD11b promoter operably linked to a nucleic acid encoding one or more therapeutic polypeptides, to vectors, cells, and/or compositions comprising the same, and to methods of their use.

Methods for the treatment and prevention of laminopathies and diseases characterised by hyperlipidemia through LING complex inhibition are disclosed. In particular, LING complex disruption by expression of dominant-negative LING complex proteins alleviates pathophysiology in Lmna mutation-associated muscular dystrophy, progeria, and dilated cardiomyopathy. In addition, LING complex disruption by expression of dominant-negative LING complex proteins also alleviates pathophysiology in mouse models of atherosclerosis and familial hypercholesterolemia.

Described herein are compositions comprising AAV vectors comprising a sequence encoding mucolipin 1, and methods of use thereof for gene therapy of Mucolipidosis IV (MLIV).