Provided are improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. Also provided are improved gene therapy methods for treating hematopoietic-related disorders. Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

Methods of identifying canine subjects having an increased likelihood of developing elevated levels of 4-ethylphenyl sulfate, canine stress, canine anxiety and/or an inhibition of growth of beneficial microbes and promotion of growth of harmful microbes are disclosed. Methods comprise analyzing a biological sample obtained from the canine subject for the presence of two copies of a minor allele of the single nucleotide polymorphism BICF2P1175095 in a canine subject. Methods of treating the identified canine subjects by administering an effective amount of tomato pomace are also disclosed. Methods of treating canine subjects for elevated 4-EPS levels, canine anxiety or canine stress are disclosed. Canine food compositions that comprises tomato pomace are disclosed.

Methods of analyzing a biological sample obtained from the canine subject for the presence of one or two copies one or two copies of minor allele T of SNP Affx-206229307; or one or two copies of minor allele A of SNP Affx-206560187; or one or two copies of minor allele T of SNP Affx-206229307 and one or two copies of minor allele A of SNP Affx-206560187 are disclosed. The methods are used in methods to identify a canine subject that has an increased likelihood or risk of hypothyroidism and in methods of treating a canine subject to reduce risk of hypothyroidism or to treat a canine subject that has hypothyroidism. The treatments comprise administering to the canine subject a low arginine diet and/or comprising an effective amount of a composition comprising a protein source, a carbohydrate source, a vegetable source, and a fruit source. Canine food compositions are disclosed.

A method of preparing a chimeric virus comprising bocavirus capsid protein (VP) and a recombinant adeno-associated (AAV) viral genome, and isolated mutant bocavirus genomes, are provided.

The present invention relates generally to polypeptides or nucleic acids for use in the treatment, management, retardation of progression or normalisation of development of an iduronate-2-sulfatase (IDS) deficiency and/or Mucopolysaccharidosis type II (MPS II) in an individual, wherein the polypeptides comprise iduronate-2-sulfatase (IDS) tethered to a tandem repeat of Apolipoprotein E (ApoEII) or the nucleic acids comprise an iduronate-2-sulfatase (IDS) gene sequence tethered to a tandem repeat of the Apolipoprotein E (ApoEII) gene sequence. The invention also relates to haematopoietic stem and progenitor cells (HSPCs) transduced by such nucleic acids for use in therapies.

The present invention relates generally to polypeptides or nucleic acids for use in the treatment, management, retardation of progression or normalisation of development of an iduronate-2-sulfatase (IDS) deficiency and/or Mucopolysaccharidosis type II (MPS II) in an individual, wherein the polypeptides comprise iduronate-2-sulfatase (IDS) tethered to a tandem repeat of Apolipoprotein E (ApoEII) or the nucleic acids comprise an iduronate-2-sulfatase (IDS) gene sequence tethered to a tandem repeat of the Apolipoprotein E (ApoEII) gene sequence. The invention also relates to haematopoietic stem and progenitor cells (HSPCs) transduced by such nucleic acids for use in therapies.

The present invention provides for methods to obtain multiple information-rich samples at different time points from the same cell while minimally disrupting the cell. The subject matter disclosed herein is generally related to nucleic acid constructs for continuous monitoring of live cells. Specifically, the subject matter disclosed herein is directed to nucleic acid constructs that encode a fusion protein and a construct RNA sequence that induce live cells to self-report cellular contents while maintaining cell viability. The present invention may be used to monitor gene expression in single cells while maintaining cell viability.

The present invention provides for methods to obtain multiple information-rich samples at different time points from the same cell while minimally disrupting the cell. The subject matter disclosed herein is generally related to nucleic acid constructs for continuous monitoring of live cells. Specifically, the subject matter disclosed herein is directed to nucleic acid constructs that encode a fusion protein and a construct RNA sequence that induce live cells to self-report cellular contents while maintaining cell viability. The present invention may be used to monitor gene expression in single cells while maintaining cell viability.

In one aspect, described herein is an intronic recognition element for splicing modifier (iREMS) that can be recognized by a compound provided herein. In another aspect, described herein are methods for modulating the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene contains an intronic REMS, and the methods utilizing a compound described herein. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene comprises an intronic REMS, and the methods utilizing a compound described herein. In another aspect, provided herein are artificial gene constructs comprising an intronic REMS, and uses of those artificial gene constructs to modulate protein production. In another aspect, provided herein are methods for altering endogenous genes to comprise an intronic REMS, and the use of a compound described herein to modulate protein produced from such altered endogenous genes.

The compositions and methods of the invention provide compositions and methods for preferential targeting of tissues to delivery therapeutic or diagnostic agents. For example, such compounds are useful in the treatment of joint disorders those affecting articulating joints, e.g., injury-induced osteoarthritis as well as autoimmune diseases affecting joint tissue such as rheumatoid arthritis.