Disclosed herein are engineered guide RNAs, engineered polynucleotides, precursor engineered polynucleotide, vectors omprising engineered polynucleotide, nucleic acids of engineered polynucleotide, pharmaceutical compositions thereof, methods of making the engineered polynucleotides and methods of treating or preventing a disease or condition by administering above described thereof.

This invention relates generally to viral vectors and viral particles based on Anelloviruses, which can be used to deliver an agent (e.g., an exogenous effector or an endogenous effector, e.g., a therapeutic effector) to a cell (e.g., a cell in a subject to be treated therapeutically). Described herein are anellosomes, anellovectors, and compositions and uses thereof.

Novel fusion-circular RNAs (f-circRNAs) and complements thereof are provided. Diagnostic and treatment methods using f-circRNA inhibitors are provided. Non-human animals expressing exogenous f-circRNA and complements thereof are also provided.

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.

Disclosed are particles which are introduced into target cells and suppress the expression of specific genes, and a method of manufacturing such particles. More particularly, the present invention relates to DNA-RNA hybrid particles that comprise a DNA strand and an RNA strand that binds to the DNA strand through partial complementary base pairing, in which the DNA strand comprises an aptamer sequence that is able to bind to a target protein produced in a target cell, and the RNA strand comprises an siRNA sequence that binds to a target RNA in the target cell to suppress protein expression from the target RNA. Such hybrid particles are capable of effectively delivering an siRNA therapeutic agent into target cells for the treatment of disease, and have resistance against digestion by in vivo nucleases, DNase and RNase, owing to complementary binding formed between DNA and RNA strands. Also, the present invention relates to a method of manufacturing such DNA-RNA hybrid particles.

Improved DNA vaccine plasmids are disclosed that contain novel immunostimulatory RNA compositions. The improved plasmids eliminate all extraneous sequences, incorporate a novel antibiotic free short RNA based selectable marker, increase eukaryotic expression using a novel chimeric promoter, improve yield and stability during bacterial production, and improve immunostimulation. These vectors are utilized in immunization to elicit improved immune responses or therapy to induce type 1 interferon production.

Provided herein are DNA origami devices useful in the targeted delivery of biologically active entities to specific cell populations.

Circular RNA and transfer vehicles, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes a chimeric antigen receptor (CAR). In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.

Circular RNA and transfer vehicles, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes a chimeric antigen receptor (CAR). In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.

The present disclosure relates to a recombinant nucleic acid molecule of the transcriptional circular RNA and its application in protein expression. Specifically, the present disclosure relates to a recombinant nucleic acid molecule of the transcriptional circular RNA, recombinant expression vector, pre-circularized RNA, circular RNA, recombinant host cell, pharmaceutical composition and protein preparing method. The transcription product of the recombinant nucleic acid molecule in this present disclosure is a circular RNA which containing specific IRES element. IRES element can increase the protein expression level of circular RNA in eukaryotic cells, achieve efficient and persistent expression of protein. It has important application value in many fields like: Preparation of mRNA infectious disease vaccines, therapeutic mRNA tumor vaccines, mRNA-based dendritic cell tumor vaccines, mRNA-based gene therapy, mRNA-based chimeric antigen receptor T cell therapy, and protein supplement therapy.