Abstract: The present disclosure provides technologies for MYC inhibition, including, e.g. MYC fusion polypeptides and compositions comprising the same as well as methods of using the same. In particular, the present disclosure, among others, provides fusion polypeptides comprising a mutant MYC polypeptide and a repressor domain. In some embodiments, such fusion polypeptides and compositions comprising the same can be useful for inducing cancer cell apoptosis. Accordingly, in some embodiments, such fusion polypeptides and compositions comprising the same can be useful for cancer treatment.

Abstract: Disclosed herein are fusion polypeptides comprising: (i) a fragment antigen comprising an epitope of a target protein antigen; and (ii) a complement binding polypeptide. The disclosure also provides fusion polynucleotides (e.g., mRNA) encoding the same. Also disclosed herein are methods of making and using the fusion polypeptides and fusion polynucleotides of the present disclosure.

Abstract: Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

Abstract: Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

Abstract: Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising 2?-O-acetylated ribose, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

Abstract: Disclosed herein are fusion polypeptides comprising: (i) a fragment antigen comprising an epitope of a target protein antigen; and (ii) a complement binding polypeptide. The disclosure also provides fusion polynucleotides (e.g., mRNA) encoding the same. Also disclosed herein are methods of making and using the fusion polypeptides and fusion polynucleotides of the present disclosure.

Abstract: Disclosed herein is an engineered polypeptide comprising (i) a payload polypeptide, and (ii) a wild-type or engineered ?-factor prepro sequence, where the wild-type or engineered ?-factor prepro sequence is operably linked to the payload polypeptide. Also provided herein are polynucleotides encoding an engineered polypeptide of the present disclosure, as well as compositions comprising such polynucleotides or engineered polypeptides of the present disclosure. Methods of making and using the disclosed polypeptides, polynucleotides and compositions are also provided.

Abstract: Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

Abstract: Linear covalently closed vectors, and compositions and methods for making same.

Abstract: Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

Abstract: Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

Abstract: Disclosed herein are fusion polypeptides comprising: (i) a fragment antigen comprising an epitope of a target protein antigen; and (ii) a complement binding polypeptide. The disclosure also provides fusion polynucleotides (e.g., mRNA) encoding the same. Also disclosed herein are methods of making and using the fusion polypeptides and fusion polynucleotides of the present disclosure.

Abstract: Linear covalently closed vectors, and compositions and methods for making same.

Abstract: Nucleic acid expression systems for delivery of oligonucleotides, such as RNA oligonucleotides, to target cells and methods of using the same are provided herein. Exemplary nucleic acid expression systems for expression of a payload sequence include at least one composition that delivers an inhibitor of a NF-?B pathway and/or an inhibitor of an IRF pathway. Provided herein are also pharmaceutical compositions that deliver an inhibitor of a NF-?B pathway and/or an inhibitor of an IRF pathway, and methods of using the same for enhancing expression of an oligonucleotide, such as an RNA oligonucleotide.

Abstract: Compositions and methods for synthesizing an RNA product are provided herein. For example, the present disclosure provides a method of producing an RNA product comprising incubating an in vitro transcription mixture, thereby producing an RNA product that comprises a plurality of single-stranded RNA molecules. In some embodiments, an in vitro transcription mixture comprises a DNA template comprising an RNA polymerase promoter sequence operatively linked to a target sequence; at least one RNA polymerase that recognizes the RNA polymerase promoter sequence; a plurality of ribonucleotides comprising at least two different types of ribonucleotides, each type comprising a different nucleoside; and a transcription buffer comprising an osmolyte.

Abstract: Nucleic acid expression systems for delivery of RNA oligonucleotides to target cells and methods of using the same are provided herein. For example, in some embodiments, a nucleic acid expression system comprises: (i) an RNA oligonucleotide comprising a payload sequence (e.g., a Myc inhibitor), and (ii) an RNA oligonucleotide comprising a sequence that encodes a US11 polypeptide. Provided herein are also pharmaceutical compositions comprising an RNA oligonucleotide comprising a payload sequence that encodes a dominant negative variant of a Myc polypeptide or portions thereof, and a pharmaceutically acceptable carrier.

Abstract: The present disclosure provides technologies for MYC inhibition, including, e.g. MYC fusion polypeptides and compositions comprising the same as well as methods of using the same. In particular, the present disclosure, among others, provides fusion polypeptides comprising a mutant MYC polypeptide and a repressor domain. In some embodiments, such fusion polypeptides and compositions comprising the same can be useful for inducing cancer cell apoptosis. Accordingly, in some embodiments, such fusion polypeptides and compositions comprising the same can be useful for cancer treatment.

Abstract: Nucleic acid expression systems are provided herein that include a first synthetic oligonucleotide comprising a payload sequence and a second synthetic oligonucleotide comprising a sequence that encodes a helper polypeptide. Compositions (e.g., pharmaceutical compositions) comprising the nucleic acid expression systems as well as methods of using the same are also provided herein.

Abstract: Linear covalently closed vectors, and compositions and methods for making same.

Abstract: The present invention relates to mutants of Cre recombinase.