Provided are an enterovirus D68 (EV-D68) or a modified form thereof, or a nucleic acid molecule comprising a genomic sequence or cDNA sequence of the EV-D68 or a modified form thereof, or a complementary sequence of the genomic sequence or cDNA sequence, or a pharmaceutical composition comprising the EV-D68 or a modified form thereof, or the nucleic acid molecule, and use of the EV-D68 or a modified form thereof, or the nucleic acid molecule in the manufacture of a pharmaceutical composition for treating a tumor.

A recombinant oncolytic virus, a synthetic DNA sequence and applications of the virus. The recombinant oncolytic virus includes a genome and an exogenous DNA sequence inserted in the genome. The exogenous DNA sequence adapts to express a basic peptide fragment, to increase the environmental pH in a host infected by the recombinant oncolytic virus. More than 60% of amino acids in the basic peptide fragment are basic amino acids. The recombinant oncolytic virus and the synthetic DNA sequence of the disclosure are used to prepare an anti-tumor drug.

The disclosure provides a recombinant oncolytic virus, a synthetic DNA sequence and applications of the virus. The recombinant oncolytic virus includes a genome and an exogenous DNA sequence inserted in the genome. The exogenous DNA sequence adapts to express a basic peptide fragment, to increase the environmental pH in a host infected by the recombinant oncolytic virus. The basic peptide fragment includes more than 60% of basic amino acids. The recombinant oncolytic virus and the synthetic DNA sequence of the disclosure are used to prepare an anti-tumor drug.

The present application provides linear RNA precursors and constructs for preparing circular RNAs (circRNAs) comprising an effector RNA sequence, such as a coding RNA sequence. In some embodiments, the linear RNA comprises from the 5 end to the 3 end: (a) a first portion of an RNA element (e.g., an IRES), (b) an effector RNA sequence, and (c) a second portion of the RNA element, wherein the first and the second portions of the RNA element associate with each other to form a double-stranded region of at least 4 basepairs long, wherein the 5 end of the first portion of the RNA element and the 3 end of the second portion of the RNA element form a nick in the double-stranded region, and wherein an RNA ligase can ligate the nick. Also provided are methods of preparing circRNAs, circRNAs prepared thereof, and methods of using the circRNAs.

The present invention related to an infectious complementary DNA (cDNA) construct characterized in that the cDNA comprises: the cDNA of the CVB3 genomic RNA sequence of a Coxsackievirus B3 (CVB3); at least one or more microRNA target sequences (miR-TS), which are complementary to one or more microRNAs having tissue-specific expression pattern, wherein the at least one or more miR-TS are integrated immediately adjacent of the 5UTR and/or the 3UTR of the CVB3 protein coding sequence.

A CVB viral expression vector comprising a PIV5 W3A viral genome that contains mutations at amino acid residue S157 or S156 in the P/V gene and a deletion of the small hydrophobic (SH) gene of the PIV5 W3A viral genome, wherein the amino acid substitution at amino acid residue S157 or S156 comprises a substitution of serine (S) to phenylalanine (F) or asparagine (N) and wherein the SH gene has a deletion of the SH open reading frame or a deletion of an entire SH gene transcript unit. The CVB viral expression vector wherein the vector expresses a heterologous polypeptide comprising a SARS-CoV-2 spike (S), and/or nucleocapsid (N) and/or membrane (M) proteins, RSV fusion protein (F) or other antigens.

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.

A modified coxsackievirus showing improved safety and/or aggressiveness to be used for oncolytic virotherapy is provided. A modified coxsackievirus showing tissue-specific suppression of proliferation and comprising a mutated genome consisting of the genome of coxsackievirus B3 wild-type (CVB3-WT) inserted with at least one polynucleotide consisting of a target sequence of tissue-specific microRNA (miRNA) is provided. The mutated genome is preferably further inserted with the region encoding GM-CSF in an expressible form.

There are provided an expression vector into which a gene encoding parasporin (hereinafter abbreviated as PS) is inserted that can realize a pharmaceutical composition applicable to the treatment of cancer; a cell into which the expression vector is introduced; a method for expressing PS, a pharmaceutical composition; and a transformant. The expression vector contains a gene encoding parasporin. The expression vector includes viral vectors into which the gene is inserted, and the viral vectors express a PS protein. The gene encoding a PS protein has the full length or a part of PS gene, which includes PS-like genes encoding proteins that have no hemolytic properties against red blood cells and that exhibit selectively cytotoxicity to cancer cells among the Cry proteins produced by Bt bacteria and/or Bt related bacteria.

A replicating oncolytic virus vector is provided having a modified Enterovirus genome (e.g., a Poliovirus, Coxsackievirus or Echovirus genome), wherein the modified Enterovirus genome has one or more copies of one or more miRNA target sequences inserted into the UTR region (e.g., via substitution) and/or in-frame within the coding region of the Enterovirus genome. Also provided are compositions and methods for treating cancer (including for example, lung cancer).