The present invention relates to products and compositions and their uses. In particular the invention relates to nucleic acid products that interfere with the LPA gene expression or inhibit its expression, preferably for use as treatment, prevention or reduction of risk of suffering cardiovascular disease such as coronary heart disease or aortic stenosis or stroke or any other disorder, pathology or syndrome linked to elevated levels of Lp(a) particles.

Provided herein are compositions and methods involving nucleic acid nanostructures that can encapsulate cargo for use in, for example, therapeutic, diagnostic, and analytical applications. The nanostructures can have a plurality of interconnected subunits configured such that the nanostructures have a continuous torus-like structure with a closed three-dimensional cavity. Preferably, the nanostructure is a nucleic acid mazzocchio. The subunits are connected by linkers having defined lengths to constrain the nanostructure into the continuous torus-like shape. The closed three-dimensional cavity is of defined size to encapsulate any cargo of interest. Cargo can also be positioned in the open hole at the center of the nanostructure. The cargo can be a wide range of compounds including, for example, chemical drugs, small molecules, therapeutics, targeting agents, enzymes, dyes, and fluorescent molecules. As such, the disclosed nanostructures are suitable for delivery of one or more therapeutic, toxic, imaging, diagnostic, or prophylactic agents.

This invention relates to compositions and methods for treating a disease or disorder associated with premature termination codon. Certain aspects of the invention relate to polynucleotides, vectors, and host cells, and uses thereof.

The present invention relates to miRNA interference technology. More specifically the invention relates to circular miRNA sponges that carry a plurality of binding sites directed to at least two types of miRNA and separated by random, non-identical spacers, allowing for the inhibition of functional classes of m1RNAs. Preferably, the binding sites are bulged binding sites wherein each bulge is created by a one base deletion and two base mismatch at positions 9-11 nt from the 3′ end of each binding site. Preferably, each spacer is 6 to 24 nucleotides in length. Preferably, the binding sites are against miR-132 and miR-212, miR-17-5p and miR-18a-5p, or miR-20b-5p and miR-106a-5p. Construction vectors and uses of said miRNA sponges for the treatment of diseases, such as cardiomyopathy and cancer, are also disclosed.

This invention relates generally to pharmaceutical compositions and preparations of circular polyribonucleotides and uses thereof.

One aspect of the present invention relates to a small circular interfering RNA (sciRNA) comprising a sense strand and an antisense strand, each of said sense and antisense strands comprising at least one nucleic acid modification, optionally wherein the sense strand has a circular or substantially circular structure. Other aspects of the invention relate a pharmaceutical composition and a method for inhibiting the expression of a target gene in a subject using the sciRNA.

Provided are methods for editing RNA by introducing a deaminase-recruiting RNA in a host cell for deamination of an adenosine in a target RNA, deaminase-recruiting RNAs used in the RNA editing methods, compositions and kits comprising the same.

The present disclosure provides a technique for introducing an antigen receptor-encoding nucleic acid into a definite site in a nucleic acid that is contained in an immune cell of a target organism. In the technique according to the present disclosure, a vector, which contains an antigen receptor-encoding nucleic acid, and a nuclease are introduced into an immune cell. The nuclease cleaves the vector and the genome sequence of the immune cell. The vector can be configured so that, when cleaved with the nuclease, a sequence, which is an antigen receptor-encoding sequence and which is introduced by microhomology-mediated end-joining (MMEJ) at the nuclease cleavage site of the genome sequence of the immune cell, is formed.

An isolated RNA molecule includes an artificial microRNA precursor comprising in the 5′.fwdarw.3′ direction: a first terminal oligonucleotide consisting of AGGCCR (SEQ ID NO: 1) or a nucleotide sequence in which one to three nucleotides in SEQ ID NO: 1 are substituted; a passenger strand oligonucleotide; a first central oligonucleotide consisting of CYG (SEQ ID NO: 2); a second central oligonucleotide consisting of a nucleotide sequence having at least 70% homology with UUGAAUAKAAAU (SEQ ID NO: 3); a third central oligonucleotide consisting of YGG (SEQ ID NO: 4); a guide strand oligonucleotide; and a second terminal oligonucleotide consisting of UGGAYYK (SEQ ID NO: 5) or a nucleotide sequence in which one to three nucleotides in SEQ ID NO: 5 are substituted.

Disclosed herein are circular RNA s and transfer vehicles, along with related compositions and methods of treatment. The circular RNAs can comprise group I intron fragments, spacers, an IRES, duplex forming regions, and/or an expression sequence, thereby having the features of improved expression, functional stability, low immunogenicity, ease of manufacturing, and/or extended half-life compared to linear RNA. Pharmaceutical compositions comprising such circular RNAs and transfer vehicles are particularly suitable for efficient protein expression in immune cells in vivo. Also disclosed are precursor RNAs and materials useful in producing the precursor or circular RNAs, which have improved circularization efficiency and/or are compatible with effective circular RNA purification methods.