This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.

Disclosed herein are compositions and methods that involve using compositions containing one or more of ETV2, FOXC2, FLI1 and a miR-200b inhibitor for directly reprogramming somatic cells into induced vasculogenic cells both in vitro and in vivo. These compositions and methods are useful for a variety of purposes, including the development of pro-angiogenic therapies.

Polynucleotides, such as aptamers, comprising at least first one 5-position modified pyrimidine and at least one second 5-position modified pyrimidine are provided, wherein the first and second 5-position modified pyrimidines are different. Methods of selecting and using such polynucleotides, such as aptamers, are also provided.

Provided are compounds, methods, and pharmaceutical compositions for modulating SCN1A RNA and/or protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a developmental or epileptic encephalopathic disease, such as Dravet Syndrome. Such symptoms include seizures, sudden unexpected death in epilepsy, status epilepticus, behavioral and developmental delays, movement and balance dysfunctions, orthopedic conditions, motor and cognitive dysfunctions, delayed language and speech issues, visual motor integration dysfunctions, visual perception dysfunctions, executive dysfunctions, growth and nutrition issues, sleeping difficulties, chronic infections, sensory integration disorders, and dysautonomia.

The present invention relates to the field of oligonucleotide conjugates and to methods of synthesis thereof. In the present method a low-water content solvent environment allows a more efficient conjugation, reducing the amount of conjugate moiety needed and increasing the conjugation reaction speed.

Provided is a nucleoside derivative represented by the following formula (1):

##STR00001##

or a salt thereof, wherein R.sup.1 represents an alkoxy group, a hydrogen atom or a halogen atom; R.sup.2 and R.sup.4, which may be the same as or different from each other, each represents a hydrogen atom, a protective group for a hydroxyl group, a phosphate group, a protected phosphate group, or —P(═O).sub.nR.sup.5R.sup.6 in which n represents 0 or 1, R.sup.5 and R.sup.6, which may be the same as or different from each other, each represents a hydrogen atom, a hydroxyl group, a protected hydroxyl group, a mercapto group, a protected mercapto group, an alkoxy group, a cyanoalkoxy group, an amino group, or a substituted amino group, provided that when n is 1, both R.sup.5 and R.sup.6 cannot be the hydrogen atom at the same time; R.sup.3 represents —(CH.sub.2).sub.mNHR.sup.7 in which m represents an integer of 1 to 6, R.sup.7 represents a hydrogen atom, an alkyl group, an alkenyl group or a protective group for an amino group; and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group, or a substituted 2-oxo-pyrimidin-1-yl group.

Provided is a nucleoside derivative represented by the following formula (1):

##STR00001##

or a salt thereof, wherein R.sup.1 represents an alkoxy group, a hydrogen atom or a halogen atom; R.sup.2 and R.sup.4, which may be the same as or different from each other, each represents a hydrogen atom, a protective group for a hydroxyl group, a phosphate group, a protected phosphate group, or —P(═O).sub.nR.sup.5R.sup.6 in which n represents 0 or 1, R.sup.5 and R.sup.6, which may be the same as or different from each other, each represents a hydrogen atom, a hydroxyl group, a protected hydroxyl group, a mercapto group, a protected mercapto group, an alkoxy group, a cyanoalkoxy group, an amino group, or a substituted amino group, provided that when n is 1, both R.sup.5 and R.sup.6 cannot be the hydrogen atom at the same time; R.sup.3 represents —(CH.sub.2).sub.mNHR.sup.7 in which m represents an integer of 1 to 6, R.sup.7 represents a hydrogen atom, an alkyl group, an alkenyl group or a protective group for an amino group; and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group, or a substituted 2-oxo-pyrimidin-1-yl group.

Methods and compositions for modulating transforming growth factor-beta (TGFβ) biological activity in a vertebrate subject in need thereof. The methods involve administering to the vertebrate subject an effective amount of a substance capable of modulating activity of LEMD3 in the vertebrate subject to thereby modulate TGFβ biological activity in the vertebrate subject.

The present disclosure provides compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ. In some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid.