Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The present invention concerns platelets transfected with exogenous genetic material and microparticles deriving from said transfected platelets having a high percentage of transfection and able to transport and to transfect acceptor cells with genetic material and then used for example in gene and cell therapy. The invention further concerns a method for the preparation of mature platelets transfected with exogenous genetic material and microparticles deriving from said transfected platelets and microparticles deriving from said transfected mature platelets which permits to obtain high percentages of transfection.

Modified macrophage immune cells are provided for treatment of cancer and other diseases. In particular said macrophages express chimeric antigen receptors (CAR). The single chain variable fragment (scFv) may be directed against thymidine kinase 1 (TK1) or hypoxanthine guanine phosphoribosyltransferase (HPRT). The signaling domain may be derived from a Toll-like receptor (TLR).

The present invention concerns platelets transfected with exogenous genetic material and microparticles deriving from said transfected platelets having a high percentage of transfection and able to transport and to transfect acceptor cells with genetic material and then used for example in gene and cell therapy. The invention further concerns a method for the preparation of mature platelets transfected with exogenous genetic material and microparticles deriving from said transfected platelets and microparticles deriving from said transfected mature platelets which permits to obtain high percentages of transfection.

The present invention addresses the problem of providing a method for producing nicotinamide mononucleotide, that produces nicotinamide mononucleotide using a single enzyme and using nucleoside monophosphate, pyrophosphate, and nicotinamide as starting materials. This problem is solved by a nicotinamide mononucleotide production method that includes at least the following steps 1) and 2): 1) a first step of producing phosphoribosyl diphosphate by the action of substantially one enzyme on nucleoside monophosphate and pyrophosphate; and 2) a second step of producing nicotinamide mononucleotide by the action of only substantially the aforementioned one enzyme on nicotinamide and the phosphoribosyl diphosphate that is the product of the first step.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

A potent short hairpin RNA (shRNA734) directed to human Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) improves the rate of gene-modified stem cell engraftment by a conditioning and in vivo selection strategy to confer resistance to a clinically available guanine analog antimetabolite, 6TG, for efficient positive selection of gene-modified stem cells. Uses for polynucleotides comprising the shRNA734 include methods for knocking down HPRT in a cell, for conferring resistance to a guanine analog antimetabolite in a cell, for producing selectable genetically modified cells, for selecting cells genetically modified with a gene of interest from a plurality of cells, for removing cells genetically modified with a gene of interest from a plurality of cells, and for treating a subject infected with HIV.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Modified macrophage immune cells are provided for treatment of cancer and other diseases.