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.

The present disclosure includes, among other things, lipids, compositions, and methods useful for delivering a polynucleotide or oligonucleotide, e.g., viral genome.

A coxsackievirus B4 strain and application thereof are disclosed. The strain is named KM140-G01 and is preserved in China Center for Type Culture Collection (CCTCC) on Jun. 18, 2023, and the preservation number is CCTCC NO: V202356, the preservation address is Wuhan University, China. The strain is a humanized coxsackievirus B4 wild type single purified strain, and has strong virus replication capacity, good genetic stability and immunogenicity; the strain can be applied to the development of human coxsackievirus B4 vaccine production strains, and is suitable for the development of attenuated coxsackievirus B4 vaccine and inactivated coxsackievirus B4 vaccine; the method can also be used for establishing an infection model on Vero cells and suckling mice, and is used for CVB4 infection and pathogenic mechanism research, CVB4 vaccine evaluation and antiviral drug screening.

The present disclosure relates to production of recombinant RNA molecules encoding an oncolytic virus genome, such as a picornavirus, with native 5 end of the viral genome utilizing ribozymes. The present disclosure further relates to the design of corresponding DNA template and the use of the recombinant RNA molecules and/or corresponding particles for the treatment and prevention of cancer.

The present invention embraces compositions comprising at least two RNA replicons (self-amplifying RNA vectors (saRNAs or rRNAs)) that can be replicated by a replicase of a self-replicating virus, e.g., a replicase of alphavirus origin. Of the at least two replicons, at least one of which optionally comprises an open reading frame encoding for the RNA-dependent RNA polymerase or replicase that is able to replicate each of the at least two replicons. Further, each replicon comprises an open reading frame encoding for different antigens of interest, e.g., different antigens derived from the same or from different pathogenic organisms, for example the glycoprotein and nucleoprotein of Ebola virus.

The present disclosure relates to a pharmaceutical composition comprising a nucleic acid molecule of an adjuvant, a metal complex stabilizing the nucleic acid molecule, and optionally an immunogen that may be a peptide or a protein, or a composition of stabilizing the nucleic acid molecule of the adjuvant comprising the metal complex. The metal complex interacts with the nucleic acid molecule of the adjuvant and/or the immunogen so as to stabilize such pharmaceutically active ingredients, and induces continuous effectiveness of the active ingredients without degradation.