Circular RNA and methods and constructs for engineering circular RNA are disclosed. In some embodiments, the circular RNA includes the following elements arranged in the following sequence: a) a 3 Group I self-splicing intron fragment, b) an internal ribosome entry site (IRES), c) a protein coding region or noncoding region, and d) a 5 Group I self-splicing intron fragment.

Disclosed are methods and constructs for engineering circular RNA Disclosed is a vector for making circular RNA, said vector comprising the following elements operably connected to each other and arranged in the following sequence: a) a 5 homology arm, b) a 3 group I intron fragment containing a 3 splice site dinucleotide, c) an optional 5 spacer sequence, d) a protein coding or noncoding region, e) an optional 3 spacer sequence, f) a 5 Group I intron fragment containing a 5 splice site dinucleotide, and g) a 3 homology arm. This vector allows production of a circular RNA that is translatable or biologically active inside eukaryotic cells. In one embodiment, the vector can comprise the 5 spacer sequence, but not the 3 spacer sequence. In yet another embodiment, the vector can also comprise the 3 spacer sequence, but not the 5 spacer sequence.

A modified adenovirus, in particular Enadenotucirev (EnAd), armed with at least two bispecific T cell engager (BiTE?) each comprising at least two binding domains, wherein at least one of the domains is specific for a surface antigen on an immune cell of interest, such as a T-cell of interest. Also provided are a composition, such as a pharmaceutical formulation comprising the virus, use of the virus and virus formulations for treatment, such as in the treatment of cancer. The disclosure also extends to processes for preparing the virus.

An adenovirus comprising a sequence of formula (I): 5ITR-B.sub.1-B.sub.A-B.sub.2-B.sub.X-B.sub.B-B.sub.Y-B.sub.3-3ITR (I) wherein B.sub.Y comprises a transgene cassette containing four transgenes, said genes encoding a FAP-Bispecific T cell activator, CXCL10, CXCL9, and IFN. The disclosure also extends to pharmaceutical composition comprising the virus, and use of the virus or formulation in treatment

A modified adenovirus, in particular Enadenotucirev (EnAd), armed with a bispecific T cell engager (BiTE?) comprising at least two binding domains, wherein at least one of the domains is specific for a surface antigen on a T-cell of interest. Also provided are a composition, such as a pharmaceutical formulation comprising the virus, use of the virus and virus formulations for treatment, such as in the treatment of cancer. The disclosure also extends to processes for preparing the virus.

Provided are recombinant coagulation factor VIII and application use thereof. The recombinant coagulation factor VIII includes more than 80% of an amino acid sequence as shown in SEQ ID NO: 1 or SEQ ID NO: 2. Through gene modification of the B domain, the recombinant coagulation factor VIII is rich in glycosylation sites, has a good coagulation function, is easily secreted outside a cell and easily interacts with a cofactor such as thrombin (Ella). In addition, the recombinant coagulation factor VIII has a weak ability to induce an antibody response and can effectively ensure a treatment effect, reduce a risk of immune rejection and lower a treatment cost.

The disclosure provides compositions containing polynucleotides that encode a stereocilin protein under regulatory control of an outer hair cell-specific promoter, as well as two-vector systems containing the same, that can be used to promote expression of stereocilin specifically in outer hair cells. Additionally, the compositions described herein may be used for the treatment of subjects having or at risk ofdeveloping hearing loss, such as hearing loss associated with a mutation in stereocilin.

A modified adenovirus, in particular Enadenotucirev (EnAd), armed with a bispecific T cell activator comprising at least two binding domains, wherein at least one of the domains is specific for a surface antigen on a T-cell of interest. Also provided are a composition, such as a pharmaceutical formulation comprising the virus, use of the virus and virus formulations for treatment, such as in the treatment of cancer. The disclosure also extends to processes for preparing the virus.

Methods of creating mutations in genomic exons by inserting introns into the genomic exons via homologous recombination. Also, methods are provided for introducing modifications into genomic exons by inserting introns into the genomic exons via homologous recombination such that a mature mRNA transcript produced from a genomic region of the genome comprising the genomic exon does not contain the modification are provided. The methods provide for a rapid method for introducing mutations and/or modifications of any type into a mammalian cell genome.

Circular RNA and methods and constructs for engineering circular RNA are disclosed. In some embodiments, the circular RNA includes the following elements arranged in the following sequence: a) an adjacent exon sequence of a 3 Group I self-splicing intron-exon, b) an internal ribosome entry site (IRES), c) a protein coding region or noncoding region, and d) an adjacent exon sequence of a 5 Group I self-splicing intron-exon.