Provided are compositions and methods for inducing expression of human beta-globin in erythrocytes for use in prophylaxis and/or therapy of a hemoglobinopathy in an individual. The method generally entails introducing into CD34+ cells a polynucleotide encoding: i) a 5′ long terminal repeat (LTR) and a self-inactivating 3′ LTR; ii) at least one polyadenylation signal; iii) at least one promoter; iv) a globin gene locus control region (LCR); v) an ankyrin insulator element (Ank); vi) a Woodchuck Post-Regulatory Element (WPRE) configured such that the WPRE does not integrate into a target genome; and vii) a sequence that is a reverse complement of a sequence encoding human beta-globin, and can include beta-globin that has a PT87Q mutation. Intron 2 of the beta globin gene can be a complete intron. Modified erythrocyte progenitor cells, recombinant vectors and virions comprising recombinant polynucleotides, and methods of making the vectors and virions are included.

The present disclosure relates to methods and compositions for elevating and stabilizing retromer for treating and/or preventing Alzheimer's disease and other neurodegenerative disorders. Additionally, the disclosure relates to adenoviral based therapy for treating Alzheimer's disease (AD), and other neurodegenerative conditions such as Parkinson's Disease (PD), neuronal ceroid lipofuscinosis (NCL), and transmissible spongiform encephalopathies (TSEs or prion disease), multiple system atrophy (MSA), Down's syndrome, and hereditary spastic paraplegia, as well as tauopathies such as progressive supranuclear palsy (PSP), frontotemporal lobar dementia linked to chromosome 17q21-22 and its subtypes (FTLD-17/FTLD-Tau), Lewy Body Disease (LBD), amyotrophic lateral sclerosis (ALS), frontal-temporal degeneration (FTD), ALS-FTD, and chronic traumatic encephalopathy (CTE).

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 and compositions for rapid development of reporter lines utilizing safe harbor sites in iPSCS, as well as other progenitor cells, pluripotent and multipotent stem cells and differentiated cells, and multiple Lox sites are provided.

Methods and compositions for rapid development of reporter lines utilizing safe harbor sites in iPSCS, as well as other progenitor cells, pluripotent and multipotent stem cells and differentiated cells, and multiple Lox sites are provided.

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

The present invention relates to nucleic acid molecules comprising a nucleic acid sequence encoding a membrane-bound biotin mimetic peptide (BMP) or biotin acceptor peptide (BAP). The invention also relates to a method for selection of high producer cells secreting a protein of interest.

Provided are embodiments of replicative oncolytic adenovirus AD5 ApoA1 for inhibiting tumor growth and metastasis and use thereof in preparation of anti-tumor drugs. The virus can rapidly replicate in tumor cells and exert an oncolytic effect. Tumor cells infected with the virus can highly express apolipoprotein ApoA1 which can be secreted extracellularly in large quantities, significantly inhibit the invasion and metastasis of tumor cells, inhibit tumor-promoting inflammation pathways, and significantly reduce a IDO-1 which is a key molecule that leads to tumor immune escape. The virus can significantly inhibit tumor growth, inhibit tumor invasion, delay progression of cachexia and prolong the survival time of tumor-bearing mice in mice with liver cancer, breast cancer, colon cancer, or lung cancer.

The present disclosure is directed to compositions and methods for the treatment of Metabolic Liver Disorders. The compositions and methods can comprise an adeno-associated virus (AAV) piggyBac polynucleotide comprising a transgene. The transgene may comprise ornithine transcarbamylase (OTC) or methylmalonyl-CoA mutase (MUT1).

The present invention provides a method and a pharmaceutical composition for the treatment of the NDO comprising the viral expression vector carrying a transcription cassette that harbors transgene(s) inhibiting/silencing neurotransmission or synaptic transmission of afferent neurons.