The disclosure is directed to compounds that bind to a target RNA molecule, such as a TPP riboswitch, compositions comprising the compounds, and methods of making and using the same. The compounds contain two structurally different fragments that allow for binding with the target RNA at two different binding sites thereby producing a higher affinity binding ligand compared to compounds that only bind to a single RNA binding site.

The disclosure is directed to compounds that bind to a target RNA molecule, such as a TPP riboswitch, compositions comprising the compounds, and methods of making and using the same. The compounds contain two structurally different fragments that allow for binding with the target RNA at two different binding sites thereby producing a higher affinity binding ligand compared to compounds that only bind to a single RNA binding site.

An engineered vaccinia virus, a pharmaceutical composition containing the same, and methods for use in treating a subject in need using the same are provided. The engineered vaccinia virus includes a mutated viral sequence and a heterologous sequence. The mutated viral sequence is used for selective replication in tumor cells and/or activation of immune cells. The heterologous sequence encodes an immune co-stimulatory pathway activating molecule, immunomodulator gene, a truncated viral envelope gene, and/or a tumor suppressor. The heterologous sequence is stably incorporated into the genome of the engineered vaccinia virus. The pharmaceutical composition includes an effective amount of the engineered vaccinia virus and a pharmaceutical acceptable vehicle. The methods for use in treating the subject in need include administering the engineered vaccinia virus to the subject.

An engineered vaccinia virus, a pharmaceutical composition containing the same, and methods for use in treating a subject in need using the same are provided. The engineered vaccinia virus includes a mutated viral sequence and a heterologous sequence. The mutated viral sequence is used for selective replication in tumor cells and/or activation of immune cells. The heterologous sequence encodes an immune co-stimulatory pathway activating molecule, immunomodulator gene, a truncated viral envelope gene, and/or a tumor suppressor. The heterologous sequence is stably incorporated into the genome of the engineered vaccinia virus. The pharmaceutical composition includes an effective amount of the engineered vaccinia virus and a pharmaceutical acceptable vehicle. The methods for use in treating the subject in need include administering the engineered vaccinia virus to the subject.

Provided herein are methods of generating a recombinant circular RNA molecule that comprises at least one N6-methyladenosine (m.sup.6A) . The m.sup.6A-modified circRNA may be used to deliver a substance to a cell and to sequester an RNA-binding protein in a cell. Methods for modulating the immunogenicity of a circular RNA also are provided.

Provided herein are methods of generating a recombinant circular RNA molecule that comprises at least one N6-methyladenosine (m.sup.6A) . The m.sup.6A-modified circRNA may be used to deliver a substance to a cell and to sequester an RNA-binding protein in a cell. Methods for modulating the immunogenicity of a circular RNA also are provided.

The present disclosure relates to a composition comprising PIC for treatment of cancer. More particularly, the present disclosure discloses a composition for treatment of cancer comprising polyinosinic-polycytidylic acid, an antibiotic or polyamine compound, a positive ion, and optionally a virus, and the use thereof in manufacture of a medicament for treatment of cancer. No figure for publication.

The present invention provides methods of screening for proteolytically stable growth factor variants, including, for example variants of human fibroblast growth factor 1 (FGF1). The present invention also provides for FGF1 variants comprising at least one amino acid substitution, an amino acid deletion, an amino acid addition and combinations thereof, wherein the resulting FGF1 variant exhibits increased proteolytic stability as compared to wild-type FGF1, as well as related uses.

The present invention provides methods of screening for proteolytically stable growth factor variants, including, for example variants of human fibroblast growth factor 1 (FGF1). The present invention also provides for FGF1 variants comprising at least one amino acid substitution, an amino acid deletion, an amino acid addition and combinations thereof, wherein the resulting FGF1 variant exhibits increased proteolytic stability as compared to wild-type FGF1, as well as related uses.

The present invention provides a Bacillus subtilis strain selected from the group consisting of a) the strain deposited as DSM32324, b) the strain deposited as DSM32325, and c) a mutant strain of (a) or (b) which has sensitivity for ampicillin, vancomycin, gentamicin, kanamycin, streptomycin, erythromycin, clindamycin, tetracycline, and chloramphenicol; and has inhibitory activity against E. coli and Clostridium perfringens. The invention further relates to Bacillus compositions comprising at least one Bacillus subtilis strain of the invention, preferably the Bacillus subtilis strain DSM32324 and/or the Bacillus subtilis strain DSM32325, as Direct Fed Microbial (DFM), premix, animal feed additive or animal feed. The invention provides a method of improving one or more animal performance parameters selected from the group consisting of i) increased weight gain (WG), ii) lower feed conversion ratio (FCR), iii) lower necrotic enteritis lesion scoring, iv) lower necrotic enteritis frequency, v) lower necrotic enteritis mortality, vi) increased European Production Efficacy Factor (EPEF), and vii) lower mortality, by feeding a strain or a composition according to the invention to an animal.