Methods are provided for the epigenetic analysis of cell-free DNA using organic boranes to convert oxidized 5-methylcytosine residues in the cell-free DNA to dihydrouracil (DHU) residues. Cell-free DNA is contacted with an organic borane selected to successively bring about reduction, deamination, and decarboxylation of oxidized 5-methylcytosine residues such as 5-carboxylcytosine and 5-formylcytosine, resulting in DHU residues in place thereof. Following amplification, the treated cell-free DNA is sequenced, with the DHU residues read as thymine residues. Reaction mixtures, kits and additional methods are also provided, as are related methods for the epigenetic analysis of DNA, including cell-free DNA.

The present invention relates to oligonucleotide conjugates and preparation and applications thereof. In particular, the present invention relates to an oligonucleotide conjugated to a biomolecule (e.g. an antibody) and/or an agent of interest (e.g. a drug). In certain embodiments, the oligonucleotide of the present invention is a hybridized complex of a single strand oligonucleotide carrying a biomolecule and a complementary strand oligonucleotide bearing an agent of interest where the hybridized nucleotide segment acts as a linker to link the biomolecule and the agent of interest in one molecule.

The present disclosure describes a method for treating mitochondrial DNA depletion syndrome by administration of a therapeutic amount of a composition comprising a dinucleotide compound or a mixture thereof. Further described herein are compounds, compositions and methods for the treatment of TK2 deficiency.

Disclosed is a composition comprising dichloroacetic acid, a process for preparing the same and a use thereof. It has been discovered that the novel impurity is glyoxylic acid, and glyoxylic acid in dichloroacetic acid can be detected and its concentration accurately measured, by ion chromatography method.

Compositions and methods for treating cancer in a subject in need thereof are described that includes administering a therapeutically effective amount of an oligonucleotide that inhibits the binding of splicing regulator SRSF1 or SRSF2 to MDM2 exon 4 or 11.

Compositions and compounds of nucleoside phosphoramidites and modified oligonucleotides, each comprising one or more charge-neutralizing moieties according to the formula V ##STR00001##
The nucleoside phosphoramidites permit facile attachment of the neutralizing moieties on the backbones of the modified oligonucleotides. The modified oligonucleotides can be used as therapeutic agents (i.e., oligotherapeutics) for the treatment of cancer, autoimmune disorders, genetic diseases, infectious diseases, neurological diseases, inflammatory diseases, metabolic diseases and others.

Compositions and compounds of nucleoside phosphoramidites and modified oligonucleotides, each comprising one or more charge-neutralizing moieties according to the formula V ##STR00001##
The nucleoside phosphoramidites permit facile attachment of the neutralizing moieties on the backbones of the modified oligonucleotides. The modified oligonucleotides can be used as therapeutic agents (i.e., oligotherapeutics) for the treatment of cancer, autoimmune disorders, genetic diseases, infectious diseases, neurological diseases, inflammatory diseases, metabolic diseases and others.

The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions.

The invention relates to a saRNAs useful in upregulating the expression of the SIRT1 gene and therapeutic compositions comprising the saRNA. Methods of using the saRNA and the therapeutic compositions are also provided.

Described herein are novel divalent nucleobases that each bind two nucleic acid strands, matched or mismatched when incorporated into a nucleic acid or nucleic acid analog backbone (a genetic recognition reagent, or genetic recognition reagent). In one embodiment, the genetic recognition reagent is a peptide nucleic acid (PNA) or gamma PNA (γPNA) oligomer. Uses of the divalent nucleobases and monomers and genetic recognition reagents containing the divalent nucleobases also are provided.