Provided herein are recombinant circular RNA (circRNA) molecules comprising an internal ribosome entry site (IRES) operably linked to a protein-coding nucleic acid sequence. The IRES includes at least one RNA secondary structure element; and a sequence region that is complementary to an 18S ribosomal RNA (rRNA). Methods of producing a protein in a cell using the recombinant circRNA molecules are also provided.

The invention provides genetic constructs and recombinant vectors comprising such constructs. The constructs and vectors can be used in gene therapy methods for treating a range of disorders, including glaucoma and deafness, or for promoting nerve regeneration and/or survival.

Disclosed herein are recombinant polypeptides derived from FBP1 and FBP2. Also disclosed herein are recombinant expression vectors and recombinant host cells for producing the aforesaid recombinant polypeptides. The recombinant polypeptides are proven to be useful and effective in producing a picornavirus with a type I internal ribosome entry site (IRES), so as to facilitate the preparation of a viral vaccine.

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.

Methods and composition for modulating a target genome and stable integration of a transgene of interest into the genome of a cell are disclosed.

The present disclosure belongs to the technical field of bio-medicine, particularly, the present disclosure relates to a tissue-specifically expressed circular RNA molecule, a cyclization precursor RNA molecule, a recombinant nucleic acid molecule, a recombinant expression vector, a recombinant host cell, a composition, a pharmaceutical preparation and application thereof in preparation of a drug for preventing or treating diseases, as well as a method for preventing or treating diseases. The circular RNA molecule provided by the present disclosure operably links a coding region to an expression regulatory element, realizing specific high expression of a target polypeptide in target cells or target tissues, and low expression of the target polypeptide in non-target cells or non-target tissues, and having high tissue expression specificity, thereby providing a safe and effective treatment strategy for clinical targeted therapy of diseases such as tumors.

The present disclosure provides a recombinant oncolytic myxoma vims engineered to express a soluble form of an immune checkpoint protein in conjunction with a cytokine/chemokine and/or a tumor antigen. In certain aspects, the oncolytic myxoma virus is a replication competent virus such as myxoma vims. Methods of cancer treatment comprising administering the recombinant oncolytic myxoma virus expressing the soluble form of the immune checkpoint protein are also provided.

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 invention provides compositions and methods for treating diseases such as cancer. The invention also relates to methods of making improved CART cell therapies, e.g., with increased level, expression, and/or activity of a TOX family protein, e.g., a TOX2 protein. The invention further provides TOX2 protein and TOX2 modulators, and methods of use of the same in connection with CART cells.

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