WO2024031078A2 - Chimeric oncolytic viruses with tropism for poliovirus receptor - Google Patents

Abstract

The present disclosure relates to molecular engineering of chimeric picornaviruses with poliovirus receptor tropism and/or improved safety profile, which may be used for treating or preventing cancer and/or infectious diseases.

Description

CHIMERIC ONCOLYTIC VIRUSES WITH TROPISM FOR POLIOVIRUS RECEPTOR CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No. 63/370,535, filed August 5, 2022, the content of which is herein incorporated by reference in its entirety. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING [0002] The contents of the electronic sequence listing (file name: ONCR_032_01WO_SeqList_ST26.xml; file size: about 153,569 bytes; and date of created: August 3, 2023) is herein incorporated by reference in its entirety. FIELD [0003] The present disclosure generally relates to the fields of immunology, inflammation, and cancer therapeutics. More specifically, the present disclosure relates to chimeric picornaviruses with tropism for poliovirus receptor, recombinant RNA molecules encoding the chimeric viruses, and production of such recombinant RNA molecules. The disclosure further relates to the use of such viruses and/or recombinant RNA molecules for cancer treatment and vaccination. BACKGROUND [0004] Picornaviruses have high potential for clinical applications such as cancer treatment and vaccination. Many picornaviruses (e.g., coxsackievirus) are oncolytic viruses able to infect and lyse tumor cells. Direct tumor cell lysis results in not only cell death, but also the generation of an innate and adaptive immune response against tumor antigens taken up and presented by local antigen presenting cells. Therefore, oncolytic viruses combat tumor cell growth through both direct cell lysis and by promoting antigen-specific adaptive responses capable of maintaining anti-tumor responses after viral clearance. Picornaviruses such as poliovirus-1 Sabin strain have also been used as vaccines, offering immune protection for subsequent viral infections. [0005] However, clinical use of picornaviruses poses several challenges. Each oncolytic virus possesses a native tropism for certain cell surface proteins and therefore can only selectively infect cells that express those proteins. Such native tropism limits the cancer types that would respond to oncolytic virus treatment. In addition, several elements of the picornaviruses are susceptible to mutation and recombination events that might affect their clinical safety in cancer treatment and vaccination. [0006] Thus, there remain long-felt and unmet needs in the art for compositions and methods related to picornaviruses with altered tropism and/or improved safety profile for clinical applications. The present disclosure provides such compositions and methods, and more, in part through the engineering of chimeric viruses. SUMMARY [0007] In one aspect, the disclosure provides A recombinant RNA molecule encoding a viral genome of a chimeric virus derived from a coxsackievirus viral genome, wherein: i) a P1 region of the coxsackievirus viral genome is replaced with a P1 region of a poliovirus viral genome; and/or ii) a 2C region of the coxsackievirus viral genome is replaced with a 2C region of the poliovirus viral genome. [0008] In some embodiments, the P1 region of the coxsackievirus viral genome is replaced with the P1 region of the poliovirus viral genome, and wherein the P1 region of the coxsackievirus viral genome corresponds to nucleotides 714-3350 of SEQ ID NO: 1. In some embodiments, the 2C region of the coxsackievirus viral genome is replaced with the 2C region of the poliovirus viral genome, and wherein the 2C region of the coxsackievirus viral genome corresponds to nucleotides 4089-5075 of SEQ ID NO: 1. [0009] In some embodiments, the chimeric virus has poliovirus receptor (PVR) tropism. In some embodiments, the chimeric virus is capable of infecting a cell expressing a poliovirus receptor. In some embodiments, the chimeric virus is incapable of infecting a cell with no expression of a poliovirus receptor. [0010] In some embodiments, the coxsackievirus is a CVA21 strain. In some embodiments, the CVA21 strain is selected from KY strain, EF strain, and Kuykendall strain. In some embodiments, the CVA21 strain is KY strain. In some embodiments, the coxsackievirus viral genome (excluding the P1 region and the 2C region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 1 (excluding the P1 region and the 2C region). [0011] In some embodiments, the poliovirus viral genome is derived from PV1-Sabin strain. In some embodiments, the P1 region of the poliovirus viral genome corresponds to nucleotides 743-3385 of SEQ ID NO: 2. In some embodiments, the P1 region of the poliovirus viral genome consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 743-3385 of SEQ ID NO: 2. In some embodiments, the 2C region of the poliovirus viral genome corresponds to nucleotides 4124-5110 of SEQ ID NO: 2. In some embodiments, the 2C region of the poliovirus viral genome consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 4124-5110 of SEQ ID NO: 2. [0012] In some embodiments, a cis-acting replication element (CRE) in the 2C region of the poliovirus viral genome is mutated, wherein the CRE corresponds to nucleotides 4444- 4504 of SEQ ID NO: 2. In some embodiments, the mutated poliovirus CRE comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 mutations compared to SEQ ID NO: 10. In some embodiments, the mutated poliovirus CRE comprises or consists of SEQ ID NO: 4 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 4. [0013] In some embodiments, the coxsackievirus viral genome comprises a coxsackievirus CRE located between stem loop I and stem loop II of an internal ribosome entry site (IRES) region located in a 5’ untranslated region (5’ UTR) of the coxsackievirus viral genome. [0014] In one aspect, the disclosure provides a recombinant RNA molecule encoding a viral genome of a picornavirus, wherein the viral genome comprises a coxsackievirus CRE located between stem loop I and stem loop II of an internal ribosome entry site (IRES) region located in a 5’ untranslated region (5’ UTR) of the viral genome. In some embodiments, the 5’ UTR comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-713 of SEQ ID NO: 1. [0015] In some embodiments, the viral genome comprises a coxsackievirus CRE located between the position corresponding to nucleotides 119 and 120 of SEQ ID NO: 1. In some embodiments, the coxsackievirus CRE comprises or consists of SEQ ID NO: 5 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 5. In some embodiments, wherein the coxsackievirus CRE comprises or consists of SEQ ID NO: 6 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 6. In some embodiments, the coxsackievirus CRE functions as a template for the uridylylation of VPg (3B) protein. In some embodiments, the coxsackievirus CRE is the only active CRE of the viral genome. [0016] In some embodiments, the recombinant RNA molecule of the disclosure comprises one or more miRNA target sequences. In some embodiments, the recombinant RNA molecule comprises two copies of each of the miRNA target sequences. In some embodiments, the one or more miRNAs are selected from miR-124, miR-1, miR-143, miR-128, miR-219, miR-219a, miR-122, miR-204, miR-217, miR-137, miR-142, and miR-126. In some embodiments, the one or more miRNAs comprise at least one, at least two, at least three, or all four miRNAs selected from miR-1, miR-122, miR-124, and miR-137. In some embodiments, the one or more miRNAs comprise miR-124 and/or miR-122. In some embodiments, the one or more miRNA target sequences are located between stem loop I and stem loop II of an IRES region located in a 5’ UTR of the coxsackievirus viral genome. In some embodiments, the one or more miRNA target sequences flanking the 5’ and/or 3’ sides of the coxsackievirus CRE. In some embodiments, the coxsackievirus CRE and the adjacent miRNA target sequence(s) on the 5’ and/or 3’ sides are separated by 1-20 base pairs. In some embodiments, the one or more miRNA target sequences are located between stem loop VI of an IRES region located in a 5’ UTR of the coxsackievirus viral genome and the P1 region. In some embodiments, the one or more miRNA target sequences are located between the region corresponding to nucleotides 617 and 713 of SEQ ID NO: 1. In some embodiments, the one or more miRNA target sequences are located between the region corresponding to nucleotides 634 and 698 of SEQ ID NO: 1. [0017] In some embodiments, the coxsackievirus viral genome comprises a deletion or truncation of the region corresponding to nucleotides 635 and 697, inclusive of the endpoints, of SEQ ID NO: 1. In some embodiments, the truncation comprises at least 10 bp, at least 20 bp, at least 30 bp, at least 40 bp, at least 50 bp, or at least 60 bp, of the region corresponding to nucleotides 635 and 697, inclusive of the endpoints, of SEQ ID NO: 1. [0018] In some embodiments, the one or more miRNA target sequences comprise SEQ ID NO: 30, or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 30. [0019] In some embodiments, the one or more miRNA target sequences comprise SEQ ID NO: 8, or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 8. [0020] In some embodiments, the recombinant RNA molecule comprises a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 28. [0021] In one aspect, the disclosure provides a recombinant RNA molecule encoding a viral genome of a chimeric virus derived from a poliovirus viral genome, wherein an internal ribosome entry site (IRES) region of the poliovirus viral genome is replaced with an IRES region of a rhinovirus viral genome. In some embodiments, the IRES region of the poliovirus viral genome corresponds to nucleotides 111-742 of SEQ ID NO: 2. In some embodiments, the poliovirus is PV1-Sabin strain. In some embodiments, the poliovirus viral genome (excluding the IRES region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 2 (excluding the IRES region). [0022] In some embodiments, the rhinovirus viral genome is derived from human rhinovirus A30 (HRVA30). In some embodiments, the IRES region of the rhinovirus viral genome corresponds to nucleotides 111-602 of SEQ ID NO: 3. In some embodiments, the IRES region of the rhinovirus viral genome comprises or consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 111-602 of SEQ ID NO: 3. In some embodiments, the IRES region of the rhinovirus viral genome comprises or consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 120-602 of SEQ ID NO: 3. [0023] In some embodiments, compared to the poliovirus, the chimeric virus is more resistant to mutational reversion that results in higher virulence. In some embodiments, the chimeric virus has lower infectivity of neuronal cells than the poliovirus. [0024] In some embodiments, a cis-acting replication element (CRE) in the poliovirus viral genome is mutated, wherein the CRE corresponds to nucleotides 4444-4504 of SEQ ID NO: 2. In some embodiments, the mutated CRE comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 mutations compared to SEQ ID NO: 10. In some embodiments, the mutated CRE comprises or consists of SEQ ID NO: 4 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutation compared to SEQ ID NO: 4. [0025] In some embodiments, the poliovirus viral genome comprises a poliovirus CRE located between stem loop I and stem loop II of the IRES region located in the 5’ UTR of the viral genome. [0026] In one aspect, the disclosure provides a recombinant RNA molecule encoding a viral genome of a picornavirus, wherein the viral genome comprises a poliovirus CRE located between stem loop I and stem loop II of an internal ribosome entry site (IRES) region located in a 5’ untranslated region (5’ UTR) of the viral genome. In some embodiments, the IRES region comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 111-602 of SEQ ID NO: 3. In some embodiments, the IRES region comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 120-602 of SEQ ID NO: 3. In some embodiments, the 5’ UTR comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-602 of SEQ ID NO: 16. In some embodiments, the 5’ UTR comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 120-602 of SEQ ID NO: 16. [0027] In some embodiments, the viral genome comprises a poliovirus CRE located between the region corresponding to nucleotides 89 and 120 of SEQ ID NO: 16. In some embodiments, the viral genome comprises a poliovirus CRE located between the region corresponding to nucleotides 116 and 120 of SEQ ID NO: 16. In some embodiments, the viral genome comprises a poliovirus CRE replacing the sequence corresponding to nucleotides 117 and 119 of SEQ ID NO: 16.. [0028] In some embodiments, the viral genome comprises a poliovirus CRE located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. In some embodiments, the poliovirus CRE comprises or consists of SEQ ID NO: 7 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 7. In some embodiments, the poliovirus CRE comprises or consists of SEQ ID NO: 25 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 25. In some embodiments, the poliovirus CRE functions as a template for the uridylylation of VPg (3B) protein. In some embodiments, the poliovirus CRE is the only active CRE of the viral genome. [0029] In some embodiments, the recombinant RNA molecule of the disclosure comprises one or more miRNA target sequences. In some embodiments, the recombinant RNA molecule comprises two copies of each of the miRNA target sequences. In some embodiments, the one or more miRNAs are selected from miR-124, miR-1, miR-143, miR-128, miR-219, miR-219a, miR-122, miR-204, miR-217, miR-137, miR-142, and miR-126. In some embodiments, the one or more miRNAs comprise at least one, at least two, at least three, or all four miRNAs selected from miR-1, miR-122, miR-124, and miR-137. In some embodiments, the one or more miRNAs comprise miR-124 and/or miR-122. [0030] In some embodiments, the one or more miRNA target sequences are located between stem loop I and stem loop II of the IRES region. In some embodiments, the one or more miRNA target sequences are located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. In some embodiments, the poliovirus viral genome comprises the one or more miRNA target sequences flanking 5’ and/or 3’ sides of the poliovirus CRE. In some embodiments, the poliovirus CRE and the adjacent miRNA target sequence(s) on the 5’ and/or 3’ sides are separated by 1-20 base pairs. In some embodiments, the poliovirus viral genome comprises SEQ ID NO: 9 located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. [0031] In some embodiments, the poliovirus viral genome comprises SEQ ID NO: 9 located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. In some embodiments, the recombinant RNA molecule comprises a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 26. [0032] In some embodiments, the chimeric virus is oncolytic. [0033] In some embodiments, replication of the chimeric virus is reduced or attenuated in a first cell compared to replication of the chimeric virus in a second cell, wherein the expression level of the one or more miRNAs in the first cell is higher than the expression level of the one or more miRNA in the second cell. In some embodiments, the expression level of the one or more miRNAs in the first cell is at least 50% higher, at least 100% higher, at least 2-fold higher, or at least 5-fold higher, than that in the second cell. In some embodiments, the first cell is a non-cancerous cell and the second cell is a cancerous cell. [0034] In some embodiments, the recombinant RNA molecule comprises one or more payload-molecule encoding transgene(s). In some embodiments, the payload molecule(s) comprise a tumor antigen. In some embodiments, the payload molecule(s) comprise a MAGE family protein, survivin, p53 mutant, Kras mutant, or a neoantigen. In some embodiments, the payload molecule(s) comprise an immune modulatory polypeptide. [0035] In some embodiments, the recombinant RNA molecule comprises a 3’ polyA tail. In some embodiments, the polyA tail consists of about 70 adenine nucleotides in length. [0036] In some embodiments, the recombinant RNA molecule comprises a nucleic acid analogue. [0037] In one aspect, the disclosure provides a particle comprising the recombinant RNA molecule of the disclosure. In some embodiments, the particle is a virus particle. In some embodiments, the virus particle has a tropism for poliovirus receptor (PVR). In some embodiments, the virus particle is produced by the recombinant RNA molecule and transcribed protein products thereof. In some embodiments, the particle is selected from the group consisting of a nanoparticle, an exosome, a liposome, and a lipoplex. In some embodiments, the particle is a lipid nanoparticle. In some embodiments, the particle comprises a second nucleic acid molecule. In some embodiments, contacting a eukaryotic cell with the particle results in production of infectious virus particles of the chimeric virus by the cell. In some embodiments, the eukaryotic cell expresses a poliovirus receptor. [0038] In one aspect, the disclosure provides a pharmaceutical composition comprising the recombinant RNA molecule of the disclosure or the particle of the disclosure, and a pharmaceutically acceptable carrier. [0039] In one aspect, the disclosure provides a method of treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of the recombinant RNA molecule of the disclosure, the particle of the disclosure, or the pharmaceutical composition of the disclosure. [0040] In one aspect, the disclosure provides a method of killing a cancer cell, comprising exposing the cancer cell to the recombinant RNA molecule of the disclosure, the particle of the disclosure, or the pharmaceutical composition of the disclosure. [0041] In some embodiments, the cancer is colorectal cancer, gastric cancer, pancreatic cancer, or prostate cancer. In some embodiments, the cancer cell expresses a poliovirus receptor. [0042] In some embodiments, the administration comprises systemic administration. In some embodiments, the administration comprises intratumoral administration. In some embodiments, the method comprises administering an immune checkpoint inhibitor; optionally, wherein the immune checkpoint inhibitor is administered systemically. In some embodiments, the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA4 inhibitor, a LAG-3 inhibitor, and/or a TIM-3 inhibitor. In some embodiments, the method comprises the step of testing the cancer cell to ascertain that it expresses PVR. [0043] In one aspect, the disclosure provides a method of immunizing a subject against a disease, comprising administering to the subject an effective amount of the recombinant RNA molecule of the disclosure, the particle of the disclosure, or the pharmaceutical composition of the disclosure. In some embodiments, the disease is a pathogenic infection, a bacterial infection, a parasitic infection or a viral infection. In some embodiments, the disease is a viral infection; optionally wherein the disease is poliomyelitis. In some embodiments, the disease is cancer. [0044] In one aspect, the disclosure provides a recombinant DNA molecule encoding the recombinant RNA molecule of the disclosure. [0045] In some embodiments, the recombinant DNA molecule comprises, from 5’ to 3’, a promoter, a ribozyme encoding sequence, the recombinant RNA molecule encoding sequence, a polyA tail, and a restriction enzyme recognition site. [0046] In some embodiments, the recombinant DNA molecule comprises a leader sequence between the promoter and the ribozyme encoding sequence. In some embodiments, the leader sequence is less than 100 bp, less than 90bp, less than 80bp, less than 70 bp, less than 60 bp, less than 50 bp, or less than 40 bp in length. In some embodiments, the leader sequence comprises or consists of a polynucleotide sequence having at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity according to SEQ ID NO: 32 or 38. In some embodiments, the leader sequence comprises or consists of SEQ ID NO: 32 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutation(s) thereto. In some embodiments, the recombinant DNA molecule does not comprise additional nucleic acid between the promoter sequence and the leader sequence. In some embodiments, the recombinant DNA molecule does not comprise additional nucleic acid between the leader sequence and the ribozyme encoding sequence. [0047] In some embodiments, the ribozyme encoding sequence comprises or consists of a polynucleotide sequence (excluding P3 stem insert) having at least 80% identity to SEQ ID NO: 33 (excluding its P3 stem insert corresponding to nucleotides 49-54 of SEQ ID NO: 33). In some embodiments, the polynucleotide sequence (excluding P3 stem insert) is 100% identical, or has at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, or at most 11 mutations (insertions, deletions or substitutions), as compared to SEQ ID NO: 33 (excluding its P3 stem insert corresponding to nucleotides 49- 54 of SEQ ID NO: 33). In some embodiments, the ribozyme encoding sequence is 100% identical, or has at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, or at most 11 mutations (insertions, deletions or substitutions), as compared to any one of SEQ ID NO: 33-37. In some embodiments, the mutation(s) are substitution(s). In some embodiments, the ribozyme encoding sequence comprises the polynucleotides

at the positions corresponding to nucleotides 25-30 of SEQ ID NO: 33. In some embodiments, the ribozyme encoding sequence comprises the polynucleotides “TTTATT” at the positions corresponding to nucleotides 25-30 of SEQ ID NO: 33. In some embodiments, the ribozyme encoding sequence comprises the P3 stem insert of about 1-30, about 1-20, about 6-20, or about 6-10 polynucleotides in length. In some embodiments, the P3 stem insert is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 polynucleotides in length. In some embodiments, the P3 stem insert is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 polynucleotides in length. In some embodiments, the P3 stem insert comprises or consists of the polynucleotides “AGATCT” at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33. In some embodiments, the P3 stem insert comprises or consists of the polynucleotides

(SEQ ID NO: 39) at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33. In some embodiments, the P3 stem insert comprises or consists of the polynucleotides

(SEQ ID NO: 40) at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33. In some embodiments, the recombinant DNA molecule does not comprise additional nucleic acid between the ribozyme encoding sequence and the polynucleotide sequence encoding the RNA molecule. In some embodiments, cleavage at the ribozyme sequence and/or the restriction enzyme recognition site sequence produces native 5’ and/or 3’ ends of the synthetic RNA viral genome after transcription. In some embodiments, the ribozyme encoding sequence comprises or consists of SEQ ID NO: 33 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutation(s) thereto. [0048] In some embodiments, the polyA tail consists of about 70 adenine nucleotides in length. [0049] In some embodiments, the restriction enzyme recognition site consists of a BsaI restriction site of SEQ ID NO: 22. [0050] In some embodiments, the promoter comprises or consists of SEQ ID NO: 31 or a sequence having at most 3, at most 2, or at most 1 nucleotide mutation(s) thereto. [0051] In some embodiments, the recombinant DNA molecule comprises no additional nucleotides in between the promoter, the optional leader sequence, the ribozyme encoding sequence, the recombinant RNA molecule encoding sequence, the polyA tail, and/or the restriction enzyme recognition site. [0052] In some embodiments, the recombinant DNA molecule comprises a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 27 or 29. [0053] In one aspect, the disclosure provides a method of producing the recombinant RNA molecule of the disclosure, comprising transcription of a recombinant DNA molecule encoding the recombinant RNA molecule. [0054] In one aspect, the disclosure provides a method of producing a recombinant RNA molecule, comprising transcription of the recombinant DNA molecule of the disclosure. [0055] In some embodiments, the transcription comprises in vitro transcription using a T7 polymerase. [0056] In one aspect, the disclosure provides a kit, comprising the recombinant RNA molecule of the disclosure, the particle of the disclosure, or the pharmaceutical composition of the disclosure, or the recombinant DNA molecule of the disclosure. BRIEF DESCRIPTION OF THE DRAWINGS [0057] FIG.1 shows schematics of chimeric viruses of i) CVA21-KY containing PV1- Sabin P1&2C regions (“KY-PVP12C”; upper) and ii) PV1-Sabin containing HRVA30 IRES region (“PV1-S/HRVA30-IRES”; lower). The numbers above each viral construct represent the nucleotide base pair location in the final chimeric viruses. The shading and the numbers below each viral construct indicate the original nucleotide base pair location of each polynucleotide fragment used in the chimeric virus. The shorter boxes represent the untranslated regions while the taller boxes represent the protein coding regions. [0058] FIG.2 shows results of viral plaque assay of the indicated parental or chimeric viruses. [0059] FIG. 3 shows TCID50 plots of different cell lines infected by the indicated parental or chimeric viruses. [0060] FIG.4A shows lysis of different cell lines infected by the indicated virus. KO: knock-out. FIG.4B shows Western analysis of human PVR expression in different cell lines. [0061] FIG.5A and FIG.5B show Western analysis of indicated cancer cell lines for expression of PVR and infectivity by PV1-S virus. [0062] FIG.6A shows TCID50 plots of colorectal cancer cells infected by the indicated viruses. FIG.6B shows TCID50 plots of gastric cancer cells infected by the indicated viruses. FIG.6C shows TCID50 plots of prostate cancer cells infected by the indicated viruses. FIG. 6D shows TCID50 plots of pancreatic cancer cells infected by the indicated viruses. FIG.6E shows summary of TCID50 values of various cell lines infected by the indicated viruses. Tables are shaded with white to dark grey, with white boxes being most sensitive and grey to dark grey being resistant to the indicated viruses. MOI<0.5 are considered sensitive. [0063] FIG.7A shows sequences of the cis-acting replication elements (CREs). Bases changed in “mutated” or “stable” sequences are shaded. FIG. 7B shows the predicted secondary structure and the estimated Gibbs free energy value of each CRE. Darker colored bases indicate stronger structural prediction. FIG. 7C shows schematics of the CRE modifications for the indicated chimeric viruses. FIG. 7D shows schematics of type I IRES elements (adapted from Cathcart et al., Picornaviruses: Pathogenesis and Molecular Biology, Reference Module in Biomedical Research, 3rd edition). FIG. 7E shows the diagram and sequence of a stabilized CRE in the 5’UTR spacer 1 region of the PV1-S/HRVA30-IRES chimeric virus. FIG.7F shows a TCID50 plot (upper) and images of plaque assay (lower) of NCI-H1299 cells infected by the indicated PV1-S/HRVA30-IRES chimeric virus variants. [0064] FIG.8A shows the diagram and sequence of a CRE-miR target (miR-T) cassette in the 5’UTR spacer 2 region of the KY-PVP12C chimeric virus. Large print represents the inserted sequence; small print represents viral sequences flanking the miR-T insertion. For the inserted sequence, bold or underlined font represents miR-Ts, and regular font represents spacer sequences. FIG. 8B shows the diagram and sequence of a CRE-miR target (miR-T) cassette in the 5’UTR spacer 1 region of the PV1-S/HRVA30-IRES chimeric virus. Large print represents the inserted sequence; small print represents viral sequences flanking the miR-T insertion. For the inserted sequence, shaded font represents the PV1-S CRE Stable sequence, bold or underlined font represents miR-Ts, and normal font represents spacer sequences. [0065] FIG.9A shows the schematics of a KY-PVP12C chimeric virus with a modified CRE and a miR-T cassette. FIG. 9B shows the schematics of a PV1-S/HRVA30-IRES chimeric virus with a modified CRE and a miR-T cassette. [0066] FIG. 10A shows results of a plaque titer assay based on NCI-H1299 cells infected by the indicated KY-PVP12C chimeric viruses. FIG. 10B shows TCID50 plots of HeLa cells infected by the indicated KY-PVP12C chimeric viruses. [0067] FIG. 11A shows miRNA mimic assay results using a KY-PVP12C chimeric virus variant containing a miR-T 122/124 cassette. FIG. 11B shows miRNA mimic assay results using a KY-PVP12C chimeric virus variant containing a miR-T 124/137 cassette. [0068] FIG.12A shows the diagram and sequence of a miR-T cassette in the 5’ spacer 2 region of the KY-PVP12C chimeric virus. FIG. 12B shows a TCID50 plot (upper) and images of plaque assay (lower) of NCI-H1299 cells infected by the indicated KY-PVP12C chimeric virus variants. FIG. 12C shows miRNA mimic assay results using KY-PVP12C 4miR-T virus containing the miR-T 1/122/124/137 cassette. [0069] FIG. 13A shows results of a plaque titer assay based on NCI-H1299 cells infected by the indicated PV1-S/HRVA30-IRES chimeric viruses. FIG. 13B shows TCID50 plots of HeLa cells infected by the indicated PV1-S/HRVA30-IRES chimeric viruses. [0070] FIG.14 shows miRNA mimic assay results using PV1-S/HRVA30-IRES virus variant containing a miR-T 122/124 cassette. [0071] FIG.15 shows gel electrophoresis images of the in vitro transcription products and 5’ cleavage patterns of the indicated viral templates. [0072] FIG. 16A shows TCID50 infection screen results for KY-PVP12C 4miR-T. FIG.16B shows TCID50 infection screen results for PV1-S/HRVA30-IRES CREmoved. DETAILED DESCRIPTION [0073] In one aspect, the present disclosure provides chimeric picornaviruses comprising a viral genome derived from a coxsackievirus with its P1 and 2C regions replaced with those from a poliovirus. The chimeric viruses possess tropism for the poliovirus receptor and can be produced at a high titer than those without the 2C region replaced. In some embodiments, such viruses are highly potent for oncolytic treatment of various cancers including colorectal cancer, gastric cancer, pancreatic cancer, and prostate cancer. In some embodiments, such viruses can be used as vaccines. In some embodiments, such viruses comprises a defective (mutated) endogenous cis-acting replication element (CRE) located in the poliovirus-derived 2C region, and an optimized CRE is inserted in its 5’ UTR region. In some embodiments, relocation of the CRE decreases the likelihood of undesirable recombination. In some embodiments, its 5’ UTR region further comprises one or more miRNA target sequences (miR-TS). In some embodiments, such miR-TS improves the virus’ selectivity for target cells (e.g., cancer cells). [0074] In another aspect, the present disclosure provides chimeric picornaviruses comprising a viral genome derived from a poliovirus, wherein the native internal ribosome entry site (IRES) region is replaced with that from a rhinovirus. Such a replacement eliminates the possibility of harmful mutations in the native poliovirus IRES region that would create undesirable virulence. In some embodiments, the IRES is derived from human rhinovirus A30 (HRVA30). In some embodiments, such viruses can be used for oncolytic treatment of various cancers including colorectal cancer, gastric cancer, pancreatic cancer, and prostate cancer. In some embodiments, such viruses can be used as vaccines. In some embodiments, such viruses comprises a defective (mutated) endogenous cis-acting replication element (CRE) located in the 2C region, and an optimized CRE is inserted in its 5’ UTR region. In some embodiments, relocation of the CRE decreases the likelihood of undesirable recombination. In some embodiments, its 5’ UTR region further comprises one or more miRNA target sequences (miR- TS). In some embodiments, such miR-TS improves the virus’ selectivity for target cells (e.g., cancer cells). [0075] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited herein, including but not limited to patents, patent applications, articles, books, and treatises, are hereby expressly incorporated by reference in their entirety for any purpose. In the event that one or more of the incorporated documents or portions of documents define a term that contradicts that term’s definition in the application, the definition that appears in this application controls. However, mention of any reference, article, publication, patent, patent publication, and patent application cited herein is not, and should not be taken as an acknowledgment, or any form of suggestion, that they constitute valid prior art or form part of the common general knowledge in any country in the world. Definitions [0076] In the present description, any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated. It should be understood that the terms “a” and “an” as used herein refer to “one or more” of the enumerated components unless otherwise indicated. The use of the alternative (e.g., “or”) should be understood to mean either one, both, or any combination thereof of the alternatives. As used herein, the terms “include” and “comprise” are used synonymously. As used herein, “plurality” may refer to one or more components (e.g., one or more miRNA target sequences). In this application, the use of “or” means “and/or” unless stated otherwise. [0077] As used in this application, the terms “about” and “approximately” are used as equivalents. Any numerals used in this application with or without about/approximately are meant to cover any normal fluctuations appreciated by one of ordinary skill in the relevant art. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 10%, in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). In some embodiments, the term “approximately” or “about” refers to a range of values that fall within 10% in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). [0078] “Decrease” or “reduce” refers to a decrease or a reduction in a particular value of at least 5%, for example, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, or 100% as compared to a reference value. A decrease or reduction in a particular value may also be represented as a fold-change in the value compared to a reference value, for example, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500, 1000-fold, or more, decrease as compared to a reference value. [0079] “Increase” refers to an increase in a particular value of at least 5%, for example, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, 100, 200, 300, 400, 500% or more as compared to a reference value. An increase in a particular value may also be represented as a fold-change in the value compared to a reference value, for example, at least 1-fold, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500, 1000-fold or more, increase as compared to the level of a reference value. [0080] The term “sequence identity” refers to the percentage of bases or amino acids between two polynucleotide or polypeptide sequences that are the same, and in the same relative position. As such one polynucleotide or polypeptide sequence has a certain percentage of sequence identity compared to another polynucleotide or polypeptide sequence. For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. The term “reference sequence” refers to a molecule to which a test sequence is compared. Unless noted otherwise, the term “sequence identity” in the claims refers to sequence identity as calculated by Clustal Omega® version 1.2.4 using default parameters. [0081] The term “derived from” refers to a polypeptide or polynucleotide sequence that comprises all or a portion of a reference polypeptide or polynucleotide sequence. For example, an RNA polynucleotide encoding an SVV or CVA genome described herein may comprise a polynucleotide sequence derived from all or a portion of a reference SVV or CVA genome (e.g., a naturally occurring or modified SVV or CVA genome). A polypeptide or polynucleotide sequence “derived from” a reference polypeptide or polynucleotide sequence also includes polypeptide and/or polynucleotide sequences that comprise one more amino acid or nucleic acid mutations (e.g., substitutions, deletions, and/or insertions) relative to the reference polypeptide or polynucleotide sequence. [0082] “Complementary” refers to the capacity for pairing, through base stacking and specific hydrogen bonding, between two sequences comprising naturally or non-naturally occurring (e.g., modified as described above) bases (nucleotides) or analogs thereof. For example, if a base at one position of a nucleic acid is capable of hydrogen bonding with a base at the corresponding position of a target, then the bases are considered to be complementary to each other at that position. Nucleic acids can comprise universal bases, or inert abasic spacers that provide no positive or negative contribution to hydrogen bonding. Base pairings may include both canonical Watson-Crick base pairing and non-Watson-Crick base pairing (e.g., Wobble base pairing and Hoogsteen base pairing). It is understood that for complementary base pairings, adenosine-type bases (A) are complementary to thymidine-type bases (T) or uracil-type bases (U), that cytosine-type bases (C) are complementary to guanosine-type bases (G), and that universal bases such as such as 3-nitropyrrole or 5-nitroindole can hybridize to and are considered complementary to any A, C, U, or T. Nichols et al., Nature, 1994;369:492- 493 and Loakes et al., Nucleic Acids Res., 1994;22:4039-4043. Inosine (I) has also been considered in the art to be a universal base and is considered complementary to any A, C, U, or T. See Watkins and SantaLucia, Nucl. Acids Research, 2005; 33 (19): 6258-6267. [0083] An “expression cassette” or “expression construct” refers to a polynucleotide sequence operably linked to a promoter. “Operably linked” refers to a juxtaposition wherein the components so described are in a relationship permitting them to function in their intended manner. For instance, a promoter is operably linked to a polynucleotide sequence if the promoter affects the transcription or expression of the polynucleotide sequence. [0084] The term “subject” includes animals, such as mammals. In some embodiments, the mammal is a primate. In some embodiments, the mammal is a human. In some embodiments, subjects are livestock such as cattle, sheep, goats, cows, swine, and the like; or domesticated animals such as dogs and cats. In some embodiments (e.g., particularly in research contexts) subjects are rodents (e.g., mice, rats, hamsters), rabbits, primates, or swine such as inbred pigs and the like. The terms “subject” and “patient” are used interchangeably herein. [0085] “Administration” refers herein to introducing an agent or composition into a subject or contacting a composition with a cell and/or tissue. [0086] “Treating” as used herein refers to delivering an agent or composition to a subject to affect a physiologic outcome. In some embodiments, treating refers to the treatment of a disease in a mammal, e.g., in a human, including (a) inhibiting the disease, i.e., arresting disease development or preventing disease progression; (b) relieving the disease, i.e., causing regression of the disease state; and (c) curing the disease. [0087] The term “effective amount” refers to the amount of an agent or composition required to result in a particular physiological effect (e.g., an amount required to increase, activate, and/or enhance a particular physiological effect). The effective amount of a particular agent may be represented in a variety of ways based on the nature of the agent, such as mass/volume, # of cells/volume, particles/volume, (mass of the agent)/(mass of the subject), # of cells/(mass of subject), or particles/(mass of subject). The effective amount of a particular agent may also be expressed as the half-maximal effective concentration (EC₅₀), which refers to the concentration of an agent that results in a magnitude of a particular physiological response that is half-way between a reference level and a maximum response level. [0088] “Population” of cells refers to any number of cells greater than 1, but is preferably at least 1x10³ cells, at least 1x10⁴ cells, at least 1x10⁵ cells, at least 1x10⁶ cells, at least 1x10⁷ cells, at least 1x10⁸ cells, at least 1x10⁹ cells, at least 1x10¹⁰ cells, or more cells. A population of cells may refer to an in vitro population (e.g., a population of cells in culture) or an in vivo population (e.g., a population of cells residing in a particular tissue). [0089] “Effector function” refers to functions of an immune cell related to the generation, maintenance, and/or enhancement of an immune response against a target cell or target antigen. [0090] The terms “microRNA,” “miRNA,” and “miR” are used interchangeably herein and refer to small non-coding endogenous RNAs of about 18-25 nucleotides in length that regulate gene expression by directing their target messenger RNAs (mRNA) for degradation or translational repression. [0091] The term “composition” as used herein refers to a formulation of a particle (e.g., virus particle) or a recombinant RNA molecule described herein that is capable of being administered or delivered to a subject or cell. [0092] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. [0093] As used herein “pharmaceutically acceptable carrier, diluent or excipient” includes without limitation any adjuvant, carrier, excipient, glidant, sweetening agent, diluent, preservative, dye/colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, surfactant, and/or emulsifier which has been approved by the United States Food and Drug Administration as being acceptable for use in humans and/or domestic animals. [0094] The term “replication-competent viral genome” refers to a viral genome encoding all of the viral genes necessary for viral replication and production of an infectious virus particle. [0095] The term “oncolytic virus” refers to a virus that has been modified to, or naturally, preferentially infect cancer cells. [0096] The term “vector” is used herein to refer to a nucleic acid molecule capable of transferring, encoding, or transporting another nucleic acid molecule. [0097] The terms “corresponding to” or “correspond to”, as used herein in relation to the amino acid or nucleic acid position(s), refer to the position(s) in a first polypeptide/polynucleotide sequence that aligns with a given amino acid/nucleic acid in a reference polypeptide/polynucleotide sequence when the first and the reference polypeptide/polynucleotide sequences are aligned. Alignment is performed by one of skill in the art using software designed for this purpose, for example, Clustal Omega® version 1.2.4 with the default parameters for that version. [0098] As used herein, the term “ratio” when used in reference to lipid composition (e.g., as a percentage of total lipid content) refers to molar ratio, unless clearly indicated otherwise. The molar ratio as a percentage of total lipid content can also be represented by “mol %”. For example, “49:22:28.5:0.5 mol %” means a molar ratio of 49:22:28.5:0.5. [0099] The term “aliphatic” or “aliphatic group,” as used herein, means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is completely saturated or that contains one or more units of unsaturation, or a monocyclic hydrocarbon or bicyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic (also referred to herein as “carbocycle,” “cycloaliphatic,” or “cycloalkyl”), that has a single point of attachment to the rest of the molecule. Unless otherwise specified, aliphatic groups contain 1-6 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms. In other embodiments, aliphatic groups contain 1-4 aliphatic carbon atoms. In still other embodiments, aliphatic groups contain 1-3 aliphatic carbon atoms, and in yet other embodiments, aliphatic groups contain 1-2 aliphatic carbon atoms. In some embodiments, “cycloaliphatic” (or “carbocycle” or “cycloalkyl”) refers to a monocyclic C₃-C₆ hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl. [0100] The term “alkyl” as used herein is a branched or unbranched saturated hydrocarbon group having a specified number of carbon atoms. In some embodiments, alkyl refers to a branched or unbranched saturated hydrocarbon group having three carbon atoms (C₃). In some embodiments, alkyl refers to a branched or unbranched saturated hydrocarbon group having six carbon atoms (C₆). In some embodiments, the term “alkyl” includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, s-pentyl, neopentyl, and hexyl. [0101] As used herein, the term “alkylene” refers to a bivalent alkyl group. An “alkylene chain” is a polymethylene group, i.e., —(CH₂)_n—, wherein n is a positive integer, preferably from 1 to 6, from 1 to 4, from 1 to 3, from 1 to 2, or from 2 to 3. A substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms are replaced with a substituent. Suitable substituents include those described below for a substituted aliphatic group. [0102] The term “aryl” used alone or as part of a larger moiety as in “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to monocyclic and bicyclic ring systems having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains three to seven ring members. The term “aryl” may be used interchangeably with the term “aryl ring”. In certain embodiments of the present disclosure, “aryl” refers to an aromatic ring system which includes, but not limited to, phenyl, biphenyl, naphthyl, anthracyl and the like, which may bear one or more substituents. Also included within the scope of the term “aryl,” as it is used herein, is a group in which an aromatic ring is fused to one or more non-aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl, and the like. [0103] The terms “heteroaryl” and “heteroar-,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 π electrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. The term “heteroatom” refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. The terms “heteroaryl” and “heteroar-,” as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is on the heteroaromatic ring. Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-l,4-oxazin- 3(4Η)-one. A heteroaryl group may be mono- or bicyclic. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted. [0104] The term “haloaliphatic” refers to an aliphatic group that is substituted with one or more halogen atoms. [0105] The term “haloalkyl” refers to a straight or branched alkyl group that is substituted with one or more halogen atoms. [0106] The term “halogen" means F, Cl, Br, or I. [0107] As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5- to 7-membered monocyclic or 7-10-membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the term “nitrogen” includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3,4- dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or ⁺NR (as in TV- substituted pyrrolidinyl). A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical,” are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl, where the radical or point of attachment is on the heterocyclyl ring. A heterocyclyl group may be mono- or bicyclic. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted. [0108] A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical,” are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl, where the radical or point of attachment is on the heterocyclyl ring. A heterocyclyl group may be mono- or bicyclic. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted. [0109] As described herein, compounds of the disclosure may contain “optionally substituted” moieties. In general, the term “substituted,” whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this disclosure are preferably those that result in the formation of stable or chemically feasible compounds. The term “stable,” as used herein regarding compounds, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein. [0110] Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; —(CH₂)_0-4R^∘; —(CH₂)_0-4OR^∘; — O(CH₂)_0-4R°, — O— (CH₂)_0-4C(O)OR°; — (CH₂)_0-4CH(OR°)₂; — (CH₂)_0-4SR°; — (CH₂)_0-4Ph, which may be substituted with R°; — (CH₂)_0-4O(CH₂)_0-1Ph which may be substituted with R°; — CH=CHPh, which may be substituted with R°; — (CH₂)_0-4O(CH₂)_0-1-pyridyl which may be substituted with R°; — NO₂; — CN; — N₃; — (CH₂)_0-4N(R°)₂; — (CH₂)_0-4N(R°)C(0)R°; — N(R°)C(S)R°; — (CH₂)_0-4N(R°)C(O)NR° ₂; — N(R°)C(S)NR° ₂; — (CH₂)_0-4N(R°)C(O)OR°; — N(R°)N(R°)C(O)R°; — N(R°)N(R°)C(O)NR° ₂; — N(R°)N(R°)C(O)OR°; — (CH₂)_0-4C(O)R°; — C(S)R°; — (CH₂)_0-4C(O)OR°; — (CH₂)_0-4C(O)SR°; — (CH₂)_0-4C(O)OSiR° ₃; — (CH₂)_{0- 4}OC(O)R°; — OC(O)(CH₂)_0-4SR°, SC(S)SR°; — (CH₂)_0-4SC(O)R°; — (CH₂)_0-4C(O)NR° ₂; — C(S)NR° ₂; — C(S)SR°; — SC(S)SR°, — (CH₂)_0-4OC(O)NR° ₂; — C(O)N(OR°)R°; — C(O)C(O)R°; — C(O)CH₂C(O)R°; — C(NOR°)R°; — (CH₂)_0-4SSR°; — (CH₂)_0-4S(O)₂R°; — (CH₂)_0-4S(O)₂OR°; — (CH₂)_0-4OS(O)₂R°; — S(O)₂NR° ₂; — (CH₂)_0-4S(O)R°; — N(R°)S(O)₂NR° ₂; — N(R°)S(O)₂R°; — N(OR°)R°; — C(NH)NR° ₂; — P(O)₂R°; — P(O)R° ₂; — OP(O)R° ₂; — OP(O)(OR°)₂; SiR° ₃; — (C_1-4 straight or branched alkylene)O — N(R°)₂; or — (C_1-4 straight or branched alkylene)C(O)O — N(R°)₂, wherein each R° may be substituted as defined below and is independently hydrogen, C_1-6 aliphatic, — CH₂Ph, — O(CH₂)_0-1Ph, — CH₂-(5-6 membered heteroaryl ring), or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R°, taken together with their intervening atom(s), form a 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.

[0111] Suitable monovalent substituents on R° (or the ring formed by taking two independent occurrences of R° together with their intervening atoms), are independently halogen, — (CH₂)_0-2R^●, -(haloR^●), — (CH₂)_0-2OH, — (CH₂)_0-2OR^●, — (CH₂)_0-2CH(OR^●)₂; — O(haloR^●), — CN, — N₃, — (CH₂)_0-2C(O)R^●, — (CH₂)_0-2C(O)OH, — (CH₂)_0-2C(O)OR^●, — (CH₂)_0-2SR^●, — (CH₂)_0-2SH, — (CH₂)_0-2NH₂, — (CH₂)_0-2NHR^●, — (CH₂)_0-2NR^● 2, — NO₂, — SiR^● ₃, — OSiR^● ₃, — C(O)SR^●, — (C_1-4 straight or branched alkylene)C(O)OR^●, or — SSR^● wherein each R^● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently selected from C_1-4 aliphatic, — CH₂Ph, — O(CH₂)_{0- 1}Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R° include =0 and =S. [0112] Suitable divalent substituents on a saturated carbon atom of an “optionally substituted” group include the following: =O, =S, =NNR*₂, =NNHC(O)R*, =NNHC(O)OR*, =NNHS(O)₂R*, =NR*, =NOR*, — O(C(R*₂))_2-3O— , or— S(C(R*₂))_2-3S— , wherein each independent occurrence of R* is selected from hydrogen, C_1-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an

“optionally substituted” group include: — O(CR*₂)_2-3O — , wherein each independent occurrence of R* is selected from hydrogen, C_1-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0113] Suitable substituents on the aliphatic group of R* include halogen, — R^●, -

(haloR^●), OH, —OR^●, — O(haloR^●), — CN, — C(O)OH, — C(O)OR^●, — NH₂, — NHR^●, —

NR^● ₂, or -NO₂, wherein each R^● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C_1-4 aliphatic, — CH₂Ph, — O(CH₂)_0-1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0114] Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include —R^†, — NR^† ₂, — C(O)R^†, — C(O)OR^†, — C(O)C(O)R^†, — C(O)CH₂C(O)R^†, — S(O)₂R^†, — S(O)₂NR^† ₂, — C(S)NR^† ₂, — C(NH)NR^† ₂, or — N(R^†)S(O)₂R^†; wherein each R^† is independently hydrogen, C_1-6 aliphatic which may be substituted as defined below, unsubstituted — OPh, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R^† , taken together with their intervening atom(s) form an unsubstituted 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0115] Suitable substituents on the aliphatic group of R^† are independently halogen, —R^●, -(haloR^●), —OH, —OR^●, — O(haloR^●), — CN, — C(O)OH, — C(O)OR^●, — NH₂, —NHR^●, — NR^● ₂, or — NO₂, wherein each R^● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C_1-4 aliphatic, — CH₂Ph, — O(CH₂)_0-1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. [0116] As used herein, the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation but is not intended to include aryl or heteroaryl moieties, as herein defined. [0117] As used herein, the term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3- phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. [0118] Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N(C_1-4alkyl)₄ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate and aryl sulfonate. [0119] A “pharmaceutically acceptable derivative” means any non-toxic salt, ester, salt of an ester or other derivative of a compound of this disclosure that, upon administration to a recipient, is capable of providing, either directly or indirectly, a compound of this disclosure or an active metabolite or residue thereof. [0120] The recitation of a listing of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups. The recitation of an embodiment for a variable herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. [0121] Unless otherwise stated, structures depicted herein are also meant to include all enantiomeric, diastereomeric, and geometric (or conformational) forms of the structure, for example, the R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the present disclosure. Unless otherwise stated, all tautomeric forms of the compounds of the present disclosure are within the scope of the present disclosure. [0122] General methods in molecular and cellular biochemistry can be found in such standard textbooks as Molecular Cloning: A Laboratory Manual, 3rd Ed. (Sambrook et al., HaRBor Laboratory Press 2001 ); Short Protocols in Molecular Biology, 4th Ed. (Ausubel et al. eds., John Wiley & Sons 1999); Protein Methods (Bollag et al., John Wiley & Sons 1996); Nonviral Vectors for Gene Therapy (Wagner et al. eds., Academic Press 1999); Viral Vectors (Kaplift & Loewy eds., Academic Press 1995); Immunology Methods Manual (I. Lefkovits ed., Academic Press 1997); and Cell and Tissue Culture: Laboratory Procedures in Biotechnology (Doyle & Griffiths, John Wiley & Sons 1998), the disclosures of which are incorporated herein by reference. Chimeric Picornaviruses [0123] Picornaviruses such as coxsackievirus and poliovirus are promising candidates for use as oncolytic viruses and/or vaccines. Picornaviruses are positive sense (+ sense) single stranded RNA (ssRNA) viruses. The family Picornaviridae comprises various genus including Cardiovirus, Cosavirus, Enterovirus, Hepatovirus, Kobuvirus, Parechovirus, Rosavirus, Salivirus, Pasivirus, and Senecavirus. Coxsackievirus, poliovirus, and rhinovirus belong to the Enterovirus genus. [0124] In some embodiments, the present disclosure provides a recombinant RNA molecule encoding a chimeric virus (e.g., a chimeric picornavirus). In some embodiments, the chimeric virus is an oncolytic virus. In some embodiments, the recombinant RNA molecule is capable of producing an infectious, lytic virus when introduced into a cell by a non-viral delivery vehicle and does not require additional exogenous genes or proteins to be present in the cell in order to replicate and produce an infectious virus. Rather, the endogenous translational mechanisms in the host cell mediate expression of the viral proteins from the recombinant RNA molecule. The expressed viral proteins then mediate viral replication and assembly into an infectious virus particle (which may comprise a capsid protein, an envelope protein, and/or a membrane protein) comprising the viral genome. In some embodiments, the recombinant RNA molecule, when introduced into a host cell, produce a virus that can infect another host cell. [0125] In some embodiments, the recombinant RNA molecule comprises one or more nucleic acid analogues. Examples of nucleic acid analogues include 2’-O-methyl-substituted RNA, 2’-O-methoxy-ethyl bases, 2’ Fluoro bases, locked nucleic acids (LNAs), unlocked nucleic acids (UNA), bridged nucleic acids (BNA), morpholinos, and peptide nucleic acids (PNA). In some embodiments, the recombinant RNA molecule is a replicon, a RNA viral genome, an mRNA molecule, or a circular RNA molecule (circRNA). In some embodiments, the recombinant RNA molecule comprises a single stranded RNA (ssRNA) viral genome. In some embodiments, the single-stranded genome may be a positive sense or negative sense genome. [0126] In some embodiments, the viral genome of a picornaviruses comprises, from 5’ to 3’, a 5’ UTR region, a P1 region, a P2 region, a P3 region, and a 3’ UTR region. In some embodiments, the 5’ UTR comprises an IRES. In some embodiments, the P2 region comprises, from 5’ to 3’, a 2A region, a 2B region, and a 2C region. In some embodiments, the P3 region comprises, from 5’ to 3’, a 3A region, a 3B region, a 3C region, and a 3D region. In some embodiments, the viral genome comprises a polyA tail downstream (3’) of the 3’ UTR region. See, e.g., FIG.1. Poliovirus Receptor [0127] In some embodiments, the chimeric virus of the disclosure has poliovirus receptor (PVR) tropism. In some embodiments, the chimeric virus is capable of infecting a cell expressing PVR. In some embodiments, for the chimeric virus derived from a coxsackievirus, wherein the P1 region of the coxsackievirus is replaced with a P1 region from a poliovirus. In some aspects, this renders the PVR trophism of the chimeric virus. In some embodiments, the chimeric virus of the disclosure is incapable of infecting a cell without expression of poliovirus receptor. [0128] Poliovirus receptor (PVR; UniProt ID# P15151), also known as NECL5 (Nectin-like protein 5) and CD155, is a single pass type I transmembrane glycoprotein that belongs to the Nectin family of the Ig (immunoglobulin) superfamily. Most Nectin family members function as cell adhesion molecules (CAMs) located on the cell surface and involved with the binding with other cells or with the extracellular matrix (ECM). Like other Nectin members, PVR contains one Ig-like V-type domain and two Ig-like C2-type domains in the extracellular region that interacts either with other CAMs of the same kind (homophilic binding) or with other CAMs or the extracellular matrix (heterophilic binding) in a Ca²⁺- independent manner. PVR is expressed in enterocytes and gastrointestinal lymphatic tissues. The normal cellular function of PVR may involve intercellular adhesion between epithelial, endothelial, and immune cells. PVR interacts with CD226 and CD96, promoting adhesion, migration and NK-cell killing and thus efficiently priming cell-mediated tumor-specific immunity. Enhanced PVR expression in tumor cells contributes to loss of contact inhibition and increased migration. It also allows tumor cell recognition and killing by CD226- or CD96-expressing NK cells. PVR also binds the inhibitory ligand TIGIT (T-cell immunoreceptor with Ig and ITIM domains) on NK and some mature T cells, antagonizing CD226 effects. [0129] PVR is overexpressed in many solid tumors across different cancer indications, including lung, colorectal, liver, ovarian, breast, adrenal, pancreatic, uterine, head and neck, gastric and esophageal cancer. High PVR expression is associated with poor prognosis and with resistance to PD-1 blockade. Thus, viruses targeting PVR can be used for immuno- oncology therapies, both as a monotherapy and in combination with PD-1 blockers. [0130] Expression of poliovirus receptor can be determined by means known in the art for mRNA and/or protein expression. mRNA expression can be determined by northern blots, ribonuclease protection assays, PCR-based methods, sequencing methods, and the like. Protein expression can be determined by immunoblotting (e.g., western blot), immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), flow cytometry, cytometric bead array, mass spectroscopy, proteomics-based methods, and the like. [0131] Additional description of PVR and related cancer treat can be found, for example, in Brlić et al., Cell Mol Immunol.2019 Jan; 16(1): 40–52 and Wu et al., J Exp Clin Cancer Res.2021 Aug 25;40(1):267, the content of each of which is incorporated by reference in its entirety for all purposes. Chimeric virus derived from coxsackievirus [0132] In some embodiments, the recombinant RNA molecules described herein encode a viral genome of a chimeric virus derived from a coxsackievirus viral genome. In some embodiments, the chimeric virus has poliovirus receptor (PVR) tropism. [0133] In some embodiments, the coxsackievirus is selected from CVB3, CVA21, and CVA9. The viral genome sequences of exemplary coxsackieviruses are provided GenBank Reference No. M33854.1 (CVB3), GenBank Reference No. KT161266.1 (CVA21), and GenBank Reference No. D00627.1 (CVA9). In some embodiments, the coxsackievirus is a CVA21 strain. In some embodiments, the coxsackievirus is a KY strain, an EF strain, or a Kuykendall (Kuyk) strain. Exemplary sequences of the Kuykendall strain are according to GenBank Accession Number AF465515.1 or AF546702.1. Exemplary sequence of the viral genome of the EF strain is according to GenBank Accession Number EF015029.1. Exemplary sequence of the viral genome of the KY strain is according to GenBank Accession Number KY284011.1. [0134] In some embodiments, the viral genome of the chimeric virus is derived from the coxsackievirus KY strain comprising a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 1. In some embodiments, the viral genome of the chimeric virus (excluding the P1 region and the 2C region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 1 (excluding the P1 region and the 2C region). [0135] In some embodiments, the viral genome of the chimeric virus is derived from the coxsackievirus KY strain and comprises a 5’ UTR region having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-713 of SEQ ID NO: 1. [0136] In some embodiments, the viral genome of the chimeric virus is derived from the coxsackievirus KY strain and comprises a 3D region having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 5952-7340 of SEQ ID NO: 1. [0137] In some embodiments, the viral genome of the chimeric virus is derived from the coxsackievirus EF strain comprising a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 18. In some embodiments, the viral genome of the chimeric virus (excluding the P1 region and the 2C region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 18 (excluding the P1 region and the 2C region). [0138] In some embodiments, the viral genome of the chimeric virus is derived from the coxsackievirus EF strain and comprises a 5’ UTR region having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-748 of SEQ ID NO: 18. [0139] In some embodiments, the viral genome of the chimeric virus is derived from the coxsackievirus EF strain and comprises a 3D region having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 5987-7375 of SEQ ID NO: 18. [0140] In some embodiments, the viral genome of the chimeric virus is derived from the coxsackievirus Kuykendall strain comprising a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 19. In some embodiments, the viral genome of the chimeric virus (excluding the P1 region and the 2C region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 19 (excluding the P1 region and the 2C region). [0141] In some embodiments, the viral genome of the chimeric virus is derived from the coxsackievirus Kuykendall strain and comprises a 5’ UTR region having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-713 of SEQ ID NO: 19. [0142] In some embodiments, the viral genome of the chimeric virus is derived from the coxsackievirus Kuykendall strain and comprises a 3D region having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 5952-7340 of SEQ ID NO: 19. [0143] In some embodiments, the viral genome of the chimeric virus is not derived from the coxsackievirus Kuykendall strain. In some embodiments, the viral genome of the chimeric virus (excluding the P1 region and the 2C region) comprises a polynucleotide sequence having less than 95%, less than 90%, less than 85%, or less than 80% identity to SEQ ID NO: 19 (excluding the P1 region and the 2C region). [0144] In some embodiments, the viral genome of the chimeric virus is not derived from the coxsackievirus Kuykendall strain and comprises a 5’ UTR region having less than 95%, less than 90%, less than 85%, or less than 80% identity to nucleotides 1-713 of SEQ ID NO: 19. [0145] In some embodiments, the viral genome of the chimeric virus is not derived from the coxsackievirus Kuykendall strain and comprises a 3D region having less than 95%, less than 90%, less than 85%, or less than 80% identity to nucleotides 5952-7340 of SEQ ID NO: 19. [0146] In some embodiments, the chimeric virus deriving from a coxsackievirus viral genome comprises a P1 region of the coxsackievirus viral genome replaced with a P1 region of a poliovirus viral genome. In some embodiments, the P1 region of the coxsackievirus viral genome corresponds to nucleotides 714-3350 of SEQ ID NO: 1. [0147] In some embodiments, the chimeric virus deriving from a coxsackievirus viral genome comprises a 2C region of the coxsackievirus viral genome replaced with a 2C region of a poliovirus viral genome. In some embodiments, the 2C region of the coxsackievirus viral genome corresponds to nucleotides 4089-5075 of SEQ ID NO: 1. [0148] Poliovirus has three serotypes: PV-1, PV-2, and PV-3; each with a slightly different capsid protein. Capsid proteins define cellular receptor specificity and virus antigenicity. PV-1 is the most common form encountered in nature; however, all three forms are extremely infectious. [0149] In some embodiments, the P1 region and/or the 2C region of the chimeric virus viral genome are derived from PV-1. In some embodiments, the P1 region and/or the 2C region of the chimeric virus viral genome are derived from PV-2. In some embodiments, the P1 region and/or the 2C region of the chimeric virus viral genome are derived from PV-3. [0150] In some embodiments, the P1 region and/or the 2C region of the chimeric virus viral genome are derived from a poliovirus (e.g., a PV1). In some embodiments, the P1 region and/or the 2C region of the chimeric virus viral genome are derived from PV1-Sabin strain. [0151] In some embodiments, the P1 region of the poliovirus viral genome corresponds to nucleotides 743-3385 of SEQ ID NO: 2. Accordingly, in some embodiments, the chimeric virus deriving from a coxsackievirus viral genome comprises a P1 region having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 743-3385 of SEQ ID NO: 2. In some embodiments, protein products (e.g., virus capsid proteins) expressed from the P1 region confers PVR tropism for the chimeric virus. [0152] In some embodiments, the 2C region of the poliovirus viral genome corresponds to nucleotides 4124-5110 of SEQ ID NO: 2. Accordingly, in some embodiments, the chimeric virus deriving from a coxsackievirus viral genome comprises a 2C region having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 4124-5110 of SEQ ID NO: 2. In some embodiments, the protein product expressed from the 2C region improves RNA capsid packaging of the chimeric virus. In some embodiments, the chimeric virus comprising the 2C region derived from the poliovirus viral genome has at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 1-fold, at least 2-fold, at least 3-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 30-fold, at least 50-fold, or at least 100-fold improvement of RNA capsid packaging compared to a control chimeric virus that contains the 2C region derived from the original coxsackievirus viral genome [0153] In some embodiments, the viral genome comprises a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to one of SEQ ID NO: 11-15 and 28. In some embodiments, the viral genome comprises a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 28. [0154] In some embodiments, the section of the viral genome spanning P1 to 2C regions comprises or consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the sequence corresponding to the section spanning P1 to 2C regions (P1-2A-2B-2C) of one of SEQ ID NO: 11-15 and 28. In some embodiments, the section of the viral genome spanning P1 to 2C regions comprises or consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the sequence corresponding to the section spanning P1 to 2C regions (P1-2A-2B-2C) of SEQ ID NO: 28. [0155] In some embodiments, the viral genome comprises a sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-857 of SEQ ID NO: 28. In some embodiments, this section corresponds to the 5’ UTR region of the viral genome. [0156] In some embodiments, the viral genome comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-3500 of SEQ ID NO: 28. In some embodiments, this section corresponds to the 5’ UTR-P1 region of the viral genome. [0157] In some embodiments, the viral genome comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-4239 of SEQ ID NO: 28. In some embodiments, this section corresponds to the 5’ UTR-P1-2A-2B region of the viral genome. [0158] In some embodiments, the viral genome comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-5225 of SEQ ID NO: 28. In some embodiments, this section corresponds to the 5’ UTR-P1-2A-2B-2C region of the viral genome. [0159] In some embodiments, the viral genome comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-7490 of SEQ ID NO: 28. In some embodiments, this section corresponds to the 5’ UTR-P1-2A-2B-2C-P3 region of the viral genome (wherein the P3 region comprises 3A-3B-3C-3D). [0160] In some embodiments, the viral genome comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 858-5225 of SEQ ID NO: 28. In some embodiments, this section corresponds to the P1-2A-2B-2C region of the viral genome. [0161] In some embodiments, the viral genome comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 858-5225 of SEQ ID NO: 28. In some embodiments, this section corresponds to the P1-2A-2B-2C region of the viral genome. [0162] In some embodiments, the viral genome comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 858-7490 of SEQ ID NO: 28. In some embodiments, this section corresponds to the P1-2A-2B-2C-P3 region of the viral genome (wherein the P3 region comprises 3A-3B-3C-3D). Chimeric virus derived from poliovirus [0163] In some embodiments, the recombinant RNA molecules described herein encode a viral genome of a chimeric virus derived from a poliovirus viral genome. In some embodiments, the chimeric virus is more resistant to mutational reversion that results in higher virulence, compared to the corresponding parental poliovirus. In some embodiments, the mutational reversion would result in undesirable higher virulence (e.g., neurovirulence). In some embodiments, the chimeric virus has lower infectivity of neuronal cells than the corresponding parental poliovirus. [0164] In some embodiments, the poliovirus is serotype 1 (PV1). In some embodiments, the poliovirus is a PV1-Sabin strain. [0165] Poliovirus has three serotypes: PV-1, PV-2, and PV-3; each with a slightly different capsid protein. Capsid proteins define cellular receptor specificity and virus antigenicity. PV-1 is the most common form encountered in nature; however, all three forms are extremely infectious. Certain polioviruses, chimeric polioviruses, and their uses have been described previously, for examples in WO 2021091964, U.S. Pat. No. 11,331,343, U.S. Pat. No.10,799,543, U.S. Pat. No.6,696,289, and U.S. Pat. Appl. No.20200368300, the content of each of which is incorporated by reference in its entirety for all purposes. [0166] In some embodiments, the viral genome of the chimeric virus is derived from the PV1-Sabin strain comprising a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 2. In some embodiments, the viral genome of the chimeric virus (excluding the IRES region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 2 (excluding the IRES region). [0167] In some embodiments, the chimeric virus deriving from a poliovirus viral genome comprises an IRES region of the poliovirus viral genome replaced with an IRES region of a rhinovirus viral genome. In some embodiments, the IRES region of the poliovirus viral genome corresponds to nucleotides 111-742 of SEQ ID NO: 2. [0168] In some embodiments, the IRES region of the chimeric virus viral genome are derived from a human rhinovirus A30 (HRVA30). In some embodiments, the IRES region of the HRVA30 viral genome corresponds to nucleotides 111-602 of SEQ ID NO: 3. Accordingly, in some embodiments, the chimeric virus deriving from a poliovirus viral genome comprises an IRES region comprising a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 111-602 of SEQ ID NO: 3. In some embodiments, the IRES comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 120-602 of SEQ ID NO: 3. [0169] In some embodiments, the chimeric virus viral genome comprises a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 26. [0170] In some embodiments, the chimeric virus viral genome comprises a sequence at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-658 of SEQ ID NO: 26. In some embodiments, this section corresponds to the 5’ UTR region of the viral genome. [0171] In some embodiments, the chimeric virus viral genome comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-3301 of SEQ ID NO: 26. In some embodiments, this section corresponds to the 5’ UTR-P1 region of the viral genome. [0172] In some embodiments, the chimeric virus viral genome comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-5026 of SEQ ID NO: 26. In some embodiments, this section corresponds to the 5’ UTR-P1-2A-2B-2C region of the viral genome. [0173] Additional descriptions of a chimeric virus comprising the IRES region from a different rhinovirus can be found, for example, in Gromeier et al., Proc Natl Acad Sci U S A. 1996 Mar 19; 93(6): 2370–2375, the content of which is incorporated by reference in its entirety. Cis-acting replication element (CRE) [0174] Picornaviruses typically comprise one or more cis-acting replication elements (CREs). CREs function as templates for the conversion of VPg, the Viral Protein of the genome, into VPgpUpU_OH. In some embodiments, two adenosine residues in the loop of the CRE RNA structures allow the viral RNA-dependent RNA polymerase 3D^Pol to add two uridine residues to the tyrosine residue of VPg. Because VPg and/or VPgpUpU_OH prime the initiation of viral RNA replication, the CREs contribute to the asymmetric replication of viral RNA. CRE elements can be found within the viral genome of various Picornaviridae family viruses, for examples in Rhinovirus, Enterovirus, Cardioviruses, Aphthovirus, Parechovirus, and Hepatoviruses. For example, the 5′-UTR of the foot-and-mouth disease virus (FMDV) contains a short hairpin loop CRE structure upstream of the IRES which is essential for RNA genome replication. In some embodiments, the CRE has a conserved AAACA sequence in the apical loop region. In some embodiments, the CRE of the enterovirus is located in its 2C open reading frame. In some embodiments, the CRE has a characteristic 14 base loops where the 1st base is a purine, the 5th and 6th bases are A residues involved in templating the addition of uridine onto VPg, the 7th residue is a purine, and the 14th residue is a purine. Therefore, in some embodiments, the CRE has a characteristic sequence motif of

(SEQ ID NO: 20). More discussions of the CRE can be found, for example, in U.S. Pat. No.8,921,101, Steil et al., Virus Res.2009 Feb; 139(2): 240–252, and Kloc et al., Front Microbiol.2018 Mar 20;9:485, the content of each of which is incorporated by reference in its entirety for all purposes. [0175] In some embodiments, the viral genome of the chimeric virus of the disclosure comprises a non-native CRE. In some embodiments, the non-native CRE is the only active CRE in the viral genome of the chimeric virus. In some embodiments, the native CRE in the corresponding region of the chimeric virus has been mutated/deactivated. [0176] In some embodiments, the chimeric virus of the disclosure comprises a mutated CRE in the 2C region of (or derived from) the poliovirus viral genome. In some embodiments, the CRE (e.g., pre-mutation CRE) corresponds to nucleotides 4444-4504 of SEQ ID NO: 2. In some embodiments, the mutated poliovirus CRE comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 mutations compared to SEQ ID NO: 10. In some embodiments, the mutated poliovirus CRE comprises or consists of SEQ ID NO: 4 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 4. [0177] In some embodiments, the viral genome deriving from a coxsackievirus viral genome comprises a CRE located between stem loop I and stem loop II of the IRES region located in the 5’ UTR of the viral genome. In some embodiments, the CRE is inserted between the position corresponding to nucleotides 119 and 120 of SEQ ID NO: 1. In some embodiments, the CRE is a non-native CRE. In some embodiments, the CRE is a coxsackievirus CRE. In some embodiments, the CRE comprises or consists of SEQ ID NO: 5 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 5. In some embodiments, the CRE comprises or consists of SEQ ID NO: 6 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 6. In some embodiments, the CRE functions as a template for the uridylylation of VPg (3B) protein. In some embodiments, the CRE is the only active CRE of the viral genome. [0178] In some embodiments, the viral genome deriving from a poliovirus viral genome comprises a CRE located between stem loop I and stem loop II of the IRES region located in the 5’ UTR of the viral genome. In some embodiments, the CRE is inserted between the position corresponding to nucleotides 89 and 120 of SEQ ID NO: 16. In some embodiments, the CRE is inserted between the position corresponding to nucleotides 89 and 100, nucleotides 95 and 105, nucleotides 100 and 110, nucleotides 105 and 115, or nucleotides 110 and 120, of SEQ ID NO: 16. In some embodiments, the CRE is inserted between the position corresponding to nucleotides 111 and 120 of SEQ ID NO: 16. In some embodiments, the CRE is inserted between the position corresponding to nucleotides 116 and 120 of SEQ ID NO: 16. In some embodiments, the CRE is inserted between the position corresponding to nucleotides 117 and 119 of SEQ ID NO: 16. In some embodiments, the CRE is inserted between the position corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. [0179] In some embodiments, the CRE is a non-native CRE. In some embodiments, the CRE is a poliovirus CRE. In some embodiments, the CRE comprises or consists of SEQ ID NO: 7 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 7.. In some embodiments, the CRE comprises or consists of SEQ ID NO: 25 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 25. In some embodiments, the CRE functions as a template for the uridylylation of VPg (3B) protein. In some embodiments, the CRE is the only active CRE of the viral genome. [0180] In some embodiments, inactivating the endogenous CRE (or relocating the CRE to near the 5’ end) improves the safety of the engineered viral genome in clinical applications, because an undesirable viral recombination event that replaces the attenuating IRES would at the same time remove the CRE in such engineered viral genomes, rendering the resultant recombinant viral genome replication-incompetent. [0181] Additional information about CRE inactivation and/or relocation can be found, for example, in Yeh et al., Cell Host Microbe.2020 May 13;27(5):736-751.e8, the content of which is incorporated by reference in its entirety. Internal Ribosome Entry Site (IRES) [0182] Unlike cellular mRNAs, picornavirus genomes lack a 7 methyl guanosine cap at the 5’ terminus, and the highly structured 5’ end of the genome would prevent ribosome scanning. Instead, the viral genome is translated by a cap-independent mechanism driven by an internal ribosome entry site (IRES) located in the 5’ UTR of the viral genome. Typically, picornavirus translation requires a unique set of IRES transactivating factors (ITAFs) to recruit ribosomes in a cap-independent manner. [0183] Picornaviruses are broadly classified by their 5’ UTRs, including the highly structured IRES. The viral protein, genome linked (VPg) is covalently linked to the 5’ end of the RNA viral genome. Downstream of the VPg-RNA linkage is the 5’ UTR, which contains multiple secondary structures: (1) stem loop I, a cloverleaf-like structure located at the 5’ end of the viral genome, important in the initiation of RNA replication for enteroviruses and rhinoviruses; and (2) the IRES, important for viral translation via a cap-independent mechanism. The IRES of poliovirus, coxsackievirus, and rhinovirus are grouped as type I IRES (enteroviruses) with a well-known secondary structure comprising, from 5’ to 3’, stem loop II, stem loop III, stem loop IV, stem loop V, and stem loop VI. See FIG.7D, which also depicts conserved RNA structural elements including the GNRA tetraloop, A/C-rich regions, and pyrimidine-rich regions. Both canonical (e.g., eIF1A, eIF2-GTP-met, eIF3) and noncanonical (e.g., PCBP2, La, unr, PTB) proteins bind to the IRES during ribosome recruitment and assembly, allowing for translation of the viral RNA. [0184] Additional discussions about picornavirus IRES can be found, for example, in Cathcart et al., Picornaviruses: Pathogenesis and Molecular Biology, Reference Module in Biomedical Research, 3rd edition; Martinez-Salas et. al., Front Microbiol.2018 Jan 4;8:2629; Kolupaeva et al., J Biol Chem. 1998 Jul 17;273(29):18599-604; de Breyne et al., Proc Natl Acad Sci U S A.2009 Jun 9;106(23):9197-202; Ali et al., J Virol.2001 Sep;75(17):7854-63; Avanzino et al., Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):9611-9616; Pisarev et al., J Virol. 2004 May;78(9):4487-97; and Yu et al., EMBO J. 2011 Aug 26;30(21):4423-36, the content of each of which is incorporated by reference herein in its entirety. miRNA-target sequence (miR-TS) [0185] A miRNA is a naturally-occurring, small non-coding RNA molecule that is usually about 18-25 nucleotides in length and is at least partially complementary to a target mRNA sequence. In animals, genes for miRNAs are transcribed to a primary miRNA (pri- miRNA), which is double stranded and forms a stem-loop structure. Pri-miRNAs are then cleaved in the nucleus to form a 70-100 nucleotides precursor miRNA (pre-miRNA). The pre- miRNA forms a hairpin structure and is transported to the cytoplasm where it is processed by the RNase III enzyme, Dicer, into a miRNA duplex of about 18-25 nucleotides. Although either strand of the duplex may potentially act as a functional miRNA, typically one strand of the miRNA is degraded and only one strand is loaded onto the Argonaute (AGO) nuclease to produce the effector RNA-induced silencing complex (RISC) in which the miRNA and its mRNA target interact. Detailed information regarding microRNAs can be found, for example, in the miRbase online database (https://www.mirbase.org/). Additional information regarding the incorporation of miR-TS in picornaviruses can be found, for example, in WO2022/150485, WO2021/243172, US20210403950, and US20200405791, the content of each of which is incorporated by reference in its entirety for all purposes. [0186] In some embodiments, the recombinant RNA molecule comprises one or more microRNA (miRNA) target sequences (miR-TS). In some embodiments, recombinant RNA molecule comprises one or more miR-TS cassettes comprising one or more miRNA target sequences. In some embodiments, expression of one or more of the corresponding miRNAs in a cell inhibit replication of the recombinant RNA molecule and/or expression of the encoded protein in the cell. In some embodiments, the one or more miRNAs are selected from miR-124, miR-1, miR-143, miR-128, miR-219, miR-219a, miR-122, miR-204, miR-217, miR-137, miR- 142, and miR-126. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR-124 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR-1 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR-143 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR- 128 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR-219a target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR-122 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR-204 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR- 219 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR-217 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR-137 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR-142 target sequence. In some embodiments, the recombinant RNA molecule comprises one or more copies of a miR- 126 target sequence. [0187] In some embodiments, the recombinant RNA molecule comprises one or more target sequences of miR-124 and one or more target sequences of miR-122. [0188] In some embodiments, the recombinant RNA molecule comprises one or more target sequences of one or more miRNAs selected from miR-1, miR-122, miR-124, and miR- 137. In some embodiments, the recombinant RNA molecule comprises two, or at least two, target sequences of miRNAs selected from miR-1, miR-122, miR-124, and miR-137. In some embodiments, the recombinant RNA molecule comprises three, or at least three, target sequences of miRNAs selected from miR-1, miR-122, miR-124, and miR-137. [0189] In some embodiments, the recombinant RNA molecule comprises one or more target sequences of miR-1, one or more target sequences of miR-122, one or more target sequences of miR-124, and one or more target sequences of miR-137. In some embodiments, the recombinant RNA molecule comprises a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 30. In some embodiments, the recombinant RNA molecule comprises a sequence having at most 10, at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 30. In some embodiments, the recombinant RNA molecule comprises SEQ ID NO: 30. [0190] In some embodiments, the recombinant RNA molecule comprises two or more copies of the one or more miRNA target sequences. In some embodiments, the recombinant RNA molecule comprises two copies of each of the miRNA target sequences. [0191] In some embodiments, the recombinant RNA molecule comprises one or more miR-TS cassettes incorporated into the 5’ untranslated region (UTR) or 3’ UTR of the viral genome. In some embodiments, the recombinant RNA molecule comprises one or more miR- TS cassettes incorporated into the 5’ UTR or 3’ UTR of one or more essential viral genes. In some embodiments, the recombinant RNA molecule comprises one or more miR-TS cassettes incorporated into the 5’ UTR or 3’ UTR of one or more non-essential viral genes. [0192] In some embodiments, the one or more miRNA target sequences are located between stem loop I, and stem loop II of the IRES region, located in the 5’UTR of the viral genome. In some embodiments, the one or more miRNA target sequences are located between the position corresponding to nucleotides 89 and 120 of SEQ ID NO: 16. In some embodiments, the one or more miRNA target sequences are located between the position corresponding to nucleotides 89 and 100, nucleotides 95 and 105, nucleotides 100 and 110, nucleotides 105 and 115, or nucleotides 110 and 120, of SEQ ID NO: 16. In some embodiments, the one or more miRNA target sequences are located between the position corresponding to nucleotides 111 and 120 of SEQ ID NO: 16. In some embodiments, the one or more miRNA target sequences are located between the position corresponding to nucleotides 116 and 120 of SEQ ID NO: 16. In some embodiments, the one or more miRNA target sequences are located between the position corresponding to nucleotides 117 and 119 of SEQ ID NO: 16. In some embodiments, the one or more miRNA target sequences are located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. [0193] In some embodiments, the one or more miRNA target sequences flank the 5’ side of the CRE of the viral genome. In some embodiments, the one or more miRNA target sequences flank the 3’ sides of the CRE of the viral genome. In some embodiments, the one or more miRNA target sequences flank both 5’ and 3’ sides of the CRE of the viral genome. In some embodiments, the CRE and the adjacent miRNA target sequence on the 5’ and/or 3’ sides are separated by 1-20 base pairs, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 base pairs. In some embodiments, the CRE and the adjacent miRNA target sequence on the 5’ and/or 3’ sides are separated by 2-8 base pairs. In some embodiments, the CRE and the adjacent miRNA target sequence on the 5’ and/or 3’ sides are separated by 2 base pairs. In some embodiments, the CRE and the adjacent miRNA target sequence on the 5’ and/or 3’ sides are separated by 3 base pairs. In some embodiments, the CRE and the adjacent miRNA target sequence on the 5’ and/or 3’ sides are separated by 4 base pairs. In some embodiments, the CRE and the adjacent miRNA target sequence on the 5’ and/or 3’ sides are separated by 5 base pairs. In some embodiments, the CRE and the adjacent miRNA target sequence on the 5’ and/or 3’ sides are separated by 6 base pairs. In some embodiments, the CRE and the adjacent miRNA target sequence on the 5’ and/or 3’ sides are separated by 7 base pairs. In some embodiments, the CRE and the adjacent miRNA target sequence on the 5’ and/or 3’ sides are separated by 8 base pairs. [0194] In some embodiments, the one or more miRNA target sequences are located between stem loop VI of the 5’ UTR IRES region and the P1 region of the viral genome. In some embodiments, the one or more miRNA target sequences are located within the region corresponding to nucleotides 617 and 713 of SEQ ID NO: 1. In some embodiments, the viral genome of the chimeric virus deriving from the coxsackievirus comprises a deletion, or truncation, of the region corresponding to nucleotides 617 and 713, inclusive of the endpoints, of SEQ ID NO: 1. In some embodiments, the truncation comprises at least 10 bp, at least 20 bp, at least 30 bp, at least 40 bp, at least 50 bp, at least 60 bp, at least 70 bp, at least 80 bp, or at least 90 bp, of the region corresponding to nucleotides 617 and 713, inclusive of the endpoints, of SEQ ID NO: 1. In some embodiments, the one or more miRNA target sequences are located between the region corresponding to nucleotides 634 and 698 of SEQ ID NO: 1. In some embodiments, the viral genome of the chimeric virus deriving from the coxsackievirus comprises a deletion, or truncation, of the region corresponding to nucleotides 635 and 697, inclusive of the endpoints, of SEQ ID NO: 1. In some embodiments, the truncation comprises at least 10 bp, at least 20 bp, at least 30 bp, at least 40 bp, at least 50 bp, or at least 60 bp, of the region corresponding to nucleotides 635 and 697, inclusive of the endpoints, of SEQ ID NO: 1. [0195] In some embodiments, the recombinant RNA molecule comprises a miR-TS cassette having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 8. In some embodiments, the recombinant RNA molecule comprises a miR-TS cassette having at most 10, at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 8. In some embodiments, the miR-TS cassette comprises the polynucleotide sequence of SEQ ID NO: 8. [0196] In some embodiments, the miR-TS cassette comprises the polynucleotide sequence of SEQ ID NO: 9, which has an embedded CRE. In some embodiments, the miR-TS cassette is located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. [0197] In some embodiments, replication of the chimeric virus is reduced or attenuated in a first cell compared to replication of the chimeric virus in a second cell, wherein the expression level of the one or more miRNAs in the first cell is higher than the expression level of the one or more miRNA in the second cell. In some embodiments, the expression level of the one or more miRNAs in the first cell is at least 10% higher, at least 20% higher, at least 30% higher, at least 40% higher, at least 50% higher, at least 70% higher, at least 100% higher, at least 150% higher, at least 2-fold higher, at least 3-fold higher, at least 4-fold higher, at least 5-fold higher, at least 7-fold higher, at least 10-fold higher, at least 20-fold higher, at least 30- fold higher, at least 50-fold higher, at least 70-fold higher, at least 100-fold higher, at least 200- fold higher, or at least 500-fold higher, than that in the second cell. In some embodiments, the first cell is a non-cancerous cell and the second cell is a cancerous cell. PolyA Tail [0198] In some embodiments, the viral genome of the chimeric virus comprises a polyA tail. In some embodiments, the polyA tail is located downstream (3’) of the 3’ UTR region of the chimeric virus. In some embodiments, no additional nucleotides is located in between the 3’ UTR and the polyA tail. In some embodiments, the polyA consists of 10-200 adenine nucleotides in length. In some embodiments, the polyA consists of 10-30, 20-50, 30-70, 40-90, 50-110, 60-130, 70-150, 80-170, 90-190, or 100-200 adenine nucleotides in length. In some embodiments, the polyA consists of 40-100, 50-90, or 60-80 adenine nucleotides in length. In some embodiments, the polyA consists of about 70 adenine nucleotides in length. Payload Molecules [0199] In some embodiments, the recombinant RNA molecule of the disclosure comprises a heterologous polynucleotide encoding a payload molecule (i.e., a payload- molecule encoding transgene). In some embodiments, the recombinant RNA molecule drives production of a virus as well as expression of the payload molecule. In some embodiments, the viral genome of the chimeric virus comprises encodes a heterologous polynucleotide encoding a payload molecule. [0200] In some embodiments, the particles of the disclosure comprises a recombinant RNA molecule encoding the viral genome of the disclosure and further comprise a recombinant RNA polynucleotide encoding a payload molecule. In some embodiments, the particles are lipid nanoparticles and comprise a recombinant RNA molecule encoding the viral genome and further comprise a recombinant RNA polynucleotide encoding a payload molecule. In some embodiments, the recombinant RNA polynucleotide in the particle (e.g., LNP) encodes a viral genome and a payload molecule. In some embodiments, the particle (e.g., LNP) comprises 1) the recombinant RNA molecule encoding the viral genome (which may or may not encode a payload molecule) and 2) a second recombinant RNA polynucleotide encoding a payload molecule. In some embodiments, the recombinant RNA molecule encoding the viral genome and the second recombinant RNA polynucleotide encoding the payload molecule are not linked in the particle (e.g., LNP). In some embodiments, the recombinant RNA molecule encoding the viral genome and the second recombinant RNA polynucleotide encoding the payload molecule are non-covalently linked. In some embodiments, the recombinant RNA molecule encoding the viral genome and the second recombinant RNA polynucleotide encoding the payload molecule are covalently linked via a covalent bond other than a regular 3', 5' phosphodiester linkage. In some embodiments, one or more miRNA target sequences are incorporated into the 3’ or 5’ UTR of the RNA polynucleotide encoding the payload molecule. In some embodiments, one or more miRNA target sequences are inserted into the transgene encoding the payload molecule (e.g., in its 3’ UTR region). In such embodiments, translation and subsequent expression of the payload does not occur, or is substantially reduced, in cells where the corresponding miRNA is expressed. In some embodiments, the recombinant RNA polynucleotide encoding a payload molecule is a replicon. [0201] In some embodiments, the expression of the payload molecule can increase the therapeutic efficacy of the virus (e.g., the oncolytic efficacy or immune-stimulating efficacy). [0202] In some embodiments, the payload molecule is selected from IL-12, GM-CSF, CXCL10, IL-36γ, CCL21, IL-18, IL-2, CCL4, CCL5, an anti-CD3-anti-FAP BiTE, an antigen binding molecule that binds DLL3, or an antigen binding molecule that binds EpCAM. In some embodiments, the payload molecule comprises or consists of MLKL 4HB domain. In some embodiments, the payload molecule comprises or consists of Gasdermin D N-terminal fragment. In some embodiments, the payload molecule comprises or consists of Gasdermin E N-terminal fragment. In some embodiments, the payload molecule comprises or consists of HMGB1 Box B domain. In some embodiments, the payload molecule comprises or consists of SMAC/Diablo. In some embodiments, the payload molecule comprises or consists of Melittin. In some embodiments, the payload molecule comprises or consists of L-amino-acid oxidase (LAAO). In some embodiments, the payload molecule comprises or consists of disintegrin. In some embodiments, the payload molecule comprises or consists of TRAIL (TNFSF10). In some embodiments, the payload molecule comprises or consists of a nitroreductase (e.g., E. coli NfsB or NfsA). In some embodiments, the payload molecule comprises or consists of a reovirus FAST protein (e.g., ARV p14, BRV p15, or p14-p15 hybrid). In some embodiments, the payload molecule comprises or consists of a leptin/FOSL2. In some embodiments, the payload molecule comprises or consists of an α-1,3-galactosyltransferase. In some embodiments, the payload molecule comprises or consists of an adenosine deaminase 2 (ADA2). In some embodiments, the paylod molecule comprises or consists of a cytokine selected from IL-IL-36γ, IL-7, IL-12, IL-18, IL-21, IL2 or IFNγ. [0203] In some embodiments, the payload is a cytotoxic polypeptide. As used herein, a “cytotoxic polypeptide” refers to a protein capable of inducing cell death when expressed in a host cell and/or cell death of a neighboring cell when secreted by the host cell. In some embodiments, the cytotoxic polypeptide is a caspase, p53, diphtheria toxin (DT), Pseudomonas Exotoxin A (PEA), Type I ribozyme inactivating proteins (RIPs) (e.g., saporin and gelonin), Type II RIPs (e.g., ricin), Shiga-like toxin 1 (Slt1), photosensitive reactive oxygen species (e.g., killer-red). In some embodiments, the cytotoxic polypeptide is encoded by a suicide gene resulting in cell death through apoptosis, such as a caspase gene. [0204] In some embodiments, the payload is an immune modulatory polypeptide. As used herein, an “immune modulatory polypeptide” is a polypeptide capable of modulating (e.g., activating or inhibiting) a particular immune receptor and/or pathway. In some embodiments, the immune modulatory polypeptides can act on any mammalian cell including immune cells, tissue cells, and stromal cells. In some embodiments, the immune modulatory polypeptide acts on an immune cell such as a T cell, an NK cell, an NKT T cell, a B cell, a dendritic cell, a macrophage, a basophil, a mast cell, or an eosinophil. Exemplary immune modulatory polypeptides include antigen-binding molecules such as antibodies or antigen binding fragments thereof, cytokines, chemokines, soluble receptors, cell-surface receptor ligands, bipartite polypeptides, and enzymes. [0205] In some embodiments, the payload is a cytokine such as IL-1, IL-12, IL-15, IL- 18, IL-36γ, TNFα, IFNα, IFNβ, IFNγ, or TNFSF14. In some embodiments, the payload is a chemokine such as CXCL10, CXCL9, CCL21, CCL4, or CCL5. In some embodiments, the payload is a ligand for a cell-surface receptor such as an NKG2D ligand, a neuropilin ligand, Flt3 ligand, a CD47 ligand (e.g., SIRP1α). In some embodiments, the payload is a soluble receptor, such as a soluble cytokine receptor (e.g., IL-13R, TGFβR1, TGFβR2, IL-35R, IL- 15R, IL-2R, IL-12R, and interferon receptors) or a soluble innate immune receptor (e.g., Toll- like receptors, complement receptors, etc.). In some embodiments, the payload is a dominant agonist mutant of a protein involved in intracellular RNA and/or DNA sensing (e.g., a dominant agonist mutant of STING, RIG-1, or MDA-5). [0206] In some embodiments, the payload is an antigen-binding molecule such as an antibody or antigen-binding fragments thereof (e.g., a single chain variable fragment (scFv), an F(ab), etc.). In some embodiments, the antigen-binding molecule specifically binds to a cell surface receptor, such as an immune checkpoint receptor (e.g., PD-1, PD-L1, and CTLA4) or additional cell surface receptors involved in cell growth and activation (e.g., OX40, CD200R, CD47, CSF1R, TREM2, 4-1BB, CD40, and NKG2D). [0207] In some embodiments, the payload molecule is a scorpion polypeptide such as chlorotoxin, BmKn-2, neopladine 1, neopladine 2, and mauriporin. In some embodiments, the payload molecule is a snake polypeptide such as contortrostatin, apoxin-I, bothropstoxin-I, BJcuL, OHAP-1, rhodostomin, drCT-I, CTX-III, B1L, and ACTX-6. In some embodiments, the payload molecule is a spider polypeptide such as a latarcin and hyaluronidase. In some embodiments, the payload molecule is a bee polypeptide such as melittin and apamin. In some embodiments, the payload molecule is a frog polypeptide such as PsT-1, PdT-1, and PdT-2. [0208] In some embodiments, the payload molecule is an enzyme. In some embodiments, the enzyme is capable of modulating the tumor microenvironment by way of altering the extracellular matrix. In such embodiments, the enzyme may include, but is not limited to, a matrix metalloprotease (e.g., MMP9), a collagenase, a hyaluronidase, a gelatinase, or an elastase. In some embodiments, the enzyme is part of a gene directed enzyme prodrug therapy (GDEPT) system, such as herpes simplex virus thymidine kinase, cytosine deaminase, nitroreductase, carboxypeptidase G2, purine nucleoside phosphorylase, or cytochrome P450. In some embodiments, the enzyme is capable of inducing or activating cell death pathways in the target cell (e.g., a caspase). In some embodiments, the enzyme is capable of degrading an extracellular metabolite or message (e.g., adenosine deaminase or arginase or 15- Hydroxyprostaglandin Dehydrogenase). [0209] In some embodiments, the payload molecule is MLKL. In some embodiments, the payload molecule is a Gasdermin D (GSDMD). In some embodiments, the payload molecule comprises or consists of a Gasdermin E N-terminal fragment. In some embodiments, the payload molecule is a HMGB1. In some embodiments, the payload molecule is a SMAC/Diablo. In some embodiments, the payload molecule is a Melittin. In some embodiments, the payload molecule is a L-amino-acid oxidase (LAAO). In some embodiments, the payload molecule is a disintegrin. In some embodiments, the payload molecule is a TRAIL (TNFSF10). In some embodiments, the payload molecule is a nitroreductase. In some embodiments, the nitroreductase is NfsB (e.g., from E. coli). In some embodiments, the nitroreductase is NfsA (e.g., from E. coli). In some embodiments, the payload molecule is a reovirus FAST protein. In some embodiments, the reovirus FAST protein is an ARV p14, a BRV p15, or a p14-p15 hybrid. In some embodiments, the payload molecule is a Leptin/FOSL2. In some embodiments, the payload molecule is an adenosine deaminase 2 (ADA2). In some embodiments, the payload molecule is an α-1,3-galactosyltransferase. In some embodiments, the payload molecule is IL-2. In some embodiments, the payload molecule is IL-7. In some embodiments, the payload molecule is IL-12. In some embodiments, the payload molecule is IL-18. In some embodiments, the payload molecule is IL-21. In some embodiments, the payload molecule is IL-36γ. In some embodiments, the payload molecule is IFNγ. In some embodiments, the payload molecule is CCL21. [0210] In some embodiments, the payload molecule is a bipartite polypeptide. As used herein, a “bipartite polypeptide” refers to a multimeric protein comprised of a first domain capable of binding a cell surface antigen expressed on a non-cancerous effector cell and a second domain capable of binding a cell-surface antigen expressed by a target cell (e.g., a cancerous cell, a tumor cell, or an effector cell of a different type). In some embodiments, the individual polypeptide domains of a bipartite polypeptide may comprise an antibody or binding fragment thereof (e.g, a single chain variable fragment (scFv) or an F(ab)), a nanobody, a diabody, a flexibody, a DOCK-AND-LOCK^TM antibody, or a monoclonal anti-idiotypic antibody (mAb2). In some embodiments, the structure of the bipartite polypeptides may be a dual-variable domain antibody (DVD-Ig^TM), a Tandab®, a bi-specific T cell engager (BiTE^TM), a DuoBody®, or a dual affinity retargeting (DART) polypeptide. In some embodiments, the bipartite polypeptide is a BiTE. [0211] In some embodiments, the cell-surface antigen expressed on an effector cell is selected from Table 1 below. In some embodiments, the cell-surface antigen expressed on a tumor cell or effector cell is selected from Table 2 below. In some embodiments, the cell- surface antigen expressed on a tumor cell is a tumor antigen. In some embodiments, the tumor antigen is selected from CD19, EpCAM, CEA, PSMA, CD33, EGFR, Her2, EphA2, MCSP, ADAM17, PSCA, 17-A1, an NKGD2 ligand, CSF1R, FAP, GD2, DLL3, TROP2, Nectin 4, or neuropilin. In other embodiments, the antigen is a viral antigen associated with the development of cancer. In some embodiments, the viral antigen associated with the development of cancer is HBV-core (Hepatitis B core antigen), HBV-pol, HbS-Ag, HPV E6, HPV E7, Merkel cell polyoma large T antigen, or Epstein Barr virus antigen EBNA2 or BZLF1. In some embodiments, the tumor antigen is selected from those listed in Table 2. Table 1: Exemplary effector cell target antigens

Table 2: Exemplary target cell antigens

[0212] In some embodiments, the payload molecule is an antigen. In some embodiments, the antigen is a protein selected from those listed in Table 2 or a portion thereof. In some embodiments, the antigen is a tumor-associated antigen (TAA) or a portion thereof. In some embodiments, the tumor-associated antigen is expressed on the cell surface of tumor cells. In some embodiments, expression of the antigen or a portion thereof induces immune responses against tumor cells. In some embodiments, the tumor-associated antigen is selected from CD19, EpCAM, CEA, PSMA, CD33, EGFR, Her2, EphA2, MCSP, ADAM17, PSCA, 17-A1, an NKGD2 ligand, CSF1R, FAP, GD2, DLL3, neuropilin, Survivin, a p53 mutant, a Kras mutant, or a MAGE family protein. In some embodiments, the tumor-associated antigen is Survivin. In some embodiments, the tumor-associated antigen is a p53 mutant (e.g., p53 with one or more activating mutations). In some embodiments, the tumor-associated antigen is a Kras mutant (e.g., Kras with one or more activating mutations). [0213] In some embodiments, the tumor-associated antigen is a MAGE (Melanoma Antigen Gene) family protein. The MAGE family protein comprises MAGE-B1, MAGEA1, MAGEA10, MAGEA11, MAGEA12, MAGEA2B, MAGEA3, MAGEA4, MAGEA6, MAGEA8, MAGEA9, MAGEB1, MAGEB10, MAGEB16, MAGEB18, MAGEB2, MAGEB3, MAGEB4, MAGEB5, MAGEB6, MAGEB6B, MAGEC1, MAGEC2, MAGEC3, MAGED1, MAGED2, MAGED4, MAGEE1, MAGEE2, MAGEF1, MAGEH1, MAGEL2, NDN, NDNL2, or any combination thereof. In some embodiments, the tumor associated antigen is selected from the antigens in Table 2B below. In some embodiments, the recombinant RNA molecule encodes two, three, four, five or more tumor associated antigens of the disclosure. [0214] In some embodiments, the payload molecule comprises or consists of a fragment (i.e., peptide fragment) of a tumor-associated antigen (TAA) of the disclosure. In some embodiments, the fragment of the TAA has a length of about 10 amino acids (aa), about 15 aa, about 20 aa, about 30 aa, about 40 aa, about 50 aa, about 60 aa, about 70 aa, about 80 aa, about 90 aa, about 100 aa, or any values in between. In some embodiments, the fragment of the TAA has a length of at least 10 aa, at least 15 aa, at least 20 aa, at least 30 aa, at least 40 aa, at least 50 aa, at least 60 aa, at least 70 aa, at least 80 aa, at least 90 aa, or at least 100 aa. In some embodiments, the recombinant RNA molecule comprises two, three, four, five or more payload molecules each comprising or consisting of a fragment of different TAAs. In some embodiments, the recombinant RNA molecule comprises two, three, four, five or more payload molecules each comprising or consisting of different fragments of the same TAA. In some embodiments, the recombinant RNA molecule comprises two, three, four, five or more copies of the payload molecules each comprising or consisting of the same fragment of the same TAA. In some embodiments, the payload molecule comprises repeats of the same peptide fragment of the TAA, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 repeats of the same peptide fragment. Table 2B. Tumor-Associated Antigen

[0215] In some embodiments, the payload molecule comprises or consist of a tumor neoantigen. The term “tumor neoantigen” refers to a neoantigen present in a subject's tumor cell or tissue but not in the subject's corresponding normal cell or tissue. Tumor neoantigen may be a peptide or a protein. In some embodiments, the tumor neoantigen is patient-specific or subject-specific. In some embodiments, the recombinant RNA molecule encodes multiple payload molecules comprising a tumor neoantigen, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 payload molecules comprising a tumor neoantigen. In some embodiments, the recombinant RNA molecule may encode multiple copies of the same tumor neoantigen. Vaccine [0216] Antigen presenting cells, such as macrophages and dendritic cells, express poliovirus receptor and are highly susceptible to infection by type 1 strains of poliovirus. [0217] Accordingly, one aspect of the disclosure provides methods for activating antigen presenting cells, comprising introducing into the antigen presenting cells the chimeric virus of the disclosure. In some embodiments, the method comprises contacting the antigen presenting cells with the chimeric virus. In some embodiments, the method comprises contacting the antigen presenting cells with a recombinant RNA molecule encoding the chimeric virus. [0218] Another aspect of the disclosure provides a composition comprising activated antigen presenting cells comprising the chimeric virus. In some embodiments, the activated antigen presenting cells may have been infected with the chimeric virus, or transduced with a recombinant RNA molecule encoding the chimeric virus. In some embodiments, the composition further comprises an antigen. [0219] In some embodiments, cell death and lysis ensue after infection by the chimeric virus of the disclosure. In some embodiments, the chimeric virus of the disclosure infects and activates antigen presenting cells without (or with minimal) cell death and lysis. [0220] In some embodiments, the activated antigen presenting cells are in vivo. In some embodiments, the activated antigen presenting cells are in vitro or ex vivo. In some embodiments, the activated antigen presenting cells are isolated. [0221] Another aspect of the disclosure provides methods of eliciting an immune response to a vaccine composition in a subject. In some embodiments, the method comprises administering the vaccine composition to the subject. In some embodiments, the disclosure provides methods of treating or preventing a disease in a subject, comprising administering the vaccine. In some embodiments, the vaccine is a cancer vaccine, for prevention or treatment of cancer. In some embodiments, the vaccine is for preventing or treating a pathogenic infection, a bacterial infection, a parasitic infection, or a viral infection. In some embodiments, the vaccine is for preventing or treating an autoimmune disease. [0222] In some embodiments, the vaccine composition is administered by subcutaneous administration. In some embodiments, the vaccine composition is administered by intramuscular administration. In some embodiments, the vaccine composition is administered by transdermal administration. In some embodiments, the delivery comprises a depot injection, optionally employing a pharmaceutically acceptable carrier that comprises an oil, emulsion, gel, semi-solid, viscous liquid, polymer, microparticles, or the like from which the composition is gradually absorbed by surrounding tissue. These carriers may prolong the time antigen presenting cells are exposed to the antigenic or immunogenic agent, as compared to an injection that is not a depot injection. [0223] In some embodiments, the vaccine composition comprises the chimeric virus of the disclosure. In some embodiments, the vaccine composition comprises a recombinant RNA molecule encoding the chimeric virus (e.g., encapsulated in a LNP). In some embodiments, the vaccine composition further comprises an adjuvant. In some embodiments, such a vaccine composition is capable of infecting antigen presenting cells, and activating them such that an immune response is generated. In some embodiments, the vaccine composition further comprises an antigen (e.g., an immunogen) and an immune response is generated against the antigen. Accordingly, administering such a composition may vaccinate the recipient against the virus or the antigen. [0224] In some embodiments, the antigen is a tumor antigen. In some embodiments, the antigen is a pathogen antigen (e.g., bacterial antigen, parasite antigen, viral antigen). In some embodiments, the viral antigen is a poliovirus antigen. In some embodiments, the viral antigen is an antigen of a non-polio virus. In some embodiments, the antigen is an autoimmune disease antigen. [0225] In some embodiments, the antigen may be polysaccharide, carbohydrate, lipid, protein (e.g., protein, glycoprotein, lipoprotein, fragment thereof (peptide) or recombinant protein), or a nucleic acid molecule encoding an antigen (e.g., DNA, RNA, mRNA, expression vector). The antigen may be an antigen from a bacterial species, including but not limited to an antigen from Mycobacterial species (such as Mycobacteria tuberculosis or species containing cross-reactive antigens therewith such as BCG) (e.g., 32A, 39A, Ag85A, Ag85B, and TB10.4), and an antigen from Borrelia species (e.g., Borrelia burgdorferi, and Borrelia mayonii, Borrelia afzelii, and Borrelia garini) (e.g., outer surface protein A (OspA) OspB, OspC, DpbA, and Bbk32), irradiated or heat-inactivated bacteria, and chemically-inactivated bacteria. The antigen may be from a virus, including but not limited to an antigen from human immunodeficiency virus (e.g., gp120, gp41, tat, vif, rev, vpr), an antigen from respiratory syncytial virus (e.g., F glycoprotein, G glycoprotein), an antigen from influenza virus (e.g., neuraminidase, hemagglutinin), an antigen from herpes simplex virus (e.g., glycoproteins such as gB, gC, gD, and gE), an antigen from papillomavirus (e.g., L1, E6, E7), an antigen from a hepatitis virus (A, B, C), an antigen from zika virus (e.g., NS-1, E), an antigen from Chikungunya virus (e.g., NS1, E1, E2, C), irradiated or heat-inactivated virus, and chemically- inactivated virus. The antigen may be from a parasite, including but not limited to, an antigen from a Plasmodium species (e.g., MSP-1, CSP, TRAP, CyRPA), irradiated or heat-inactivated parasite, and chemically-inactivated parasite. The antigen may be a tumor antigen that comprises: a product of a mutated gene; a cell surface protein overexpressed or aberrantly expressed on tumor cells; a products of an oncogenic virus; an oncofetal antigen; a cell surface glycolipid or glycoprotein with aberrant glycosylation; a tumor cell lysate (oncolysate); a shed tumor antigen (e.g., collected from and shed into cell culture medium of cultured tumor cells, or from body fluid surrounding a tumor), exosomes from tumor cells; RNA purified from tumor cells; or nucleic acid molecules encoding a tumor antigen. In some embodiments, the tumor antigen is selected from MUC-1, alpha fetoprotein, ovarian carcinoma antigen (CA125), carcinoembryonic antigen (CEA), Lewis antigens, ganglioside N-glycolyl-GM3, tyrosinase, melanoma-associated antigen (MAGE), EGFRviii, RAGE-1, HER2 (human epidermal growth factor receptor 2), and Melan-A/MART-1. In light of dendritic cells ability to migrate into the central nervous system, an antigen may comprise an antigen associated with an autoimmune disease such as a neuroinflammatory disease such as Alzheimer's disease (e.g., peptides Aβ1- 42, Aβ1-6, Aβ1-42. Tau-peptide C-294-305, AV-1959R, AV-1980R, AV-1953R). [0226] In some embodiments, the antigen is not part of the chimeric virus. In some embodiments, the antigen is part of the chimeric virus (e.g., conjugated to the chimeric virus). In some embodiments, the antigen is encoded by the chimeric virus as a payload molecule. In some embodiments, the antigen is encoded by the recombinant RNA molecule. In some embodiments, the antigen is encoded by a second recombinant RNA molecule in the particle. Methods of producing recombinant RNA viral genomes [0227] In some embodiments, the recombinant RNA molecules of the disclosure are produced in vitro using one or more DNA vector templates comprising a polynucleotide encoding the recombinant RNA molecules. A vector may include sequences that direct autonomous replication in a cell and/or may include sequences sufficient to allow integration into host cell DNA. In some embodiments, the recombinant RNA molecule of the disclosure is produced using one or more viral vectors. [0228] In some embodiments, the recombinant RNA molecules of the disclosure are produced by introducing a polynucleotide encoding the recombinant RNA molecule (e.g., by means of transfection, transduction, electroporation, and the like) into a suitable host cell in vitro. Suitable host cells include insect and mammalian cell lines. The host cells are cultured for an appropriate amount of time to allow expression of the polynucleotides and production of the recombinant RNA molecules. The recombinant RNA molecules are then isolated from the host cell and formulated for therapeutic use (e.g., encapsulated in a particle). [0229] In some embodiments, the replication of the recombinant RNA molecules of the disclosure require discrete 5’ and/or 3’ ends. The RNA transcripts produced by T7 RNA polymerase in vitro or by mammalian RNA Pol II contain mammalian 5’ and 3’ UTRs do not contain the discrete ends. For example, the T7 RNA polymerase requires a guanosine residue on the 5’ end of the template polynucleotide in order to initiate transcription. In some embodiments, polynucleotides suitable for use in the production of the recombinant RNA molecules of the disclosure require additional non-viral 5’ and/or 3’ sequences that enable generation of the discrete 5’ and 3’ ends required for the replication of the recombinant RNA molecule. Such sequences are referred to herein as junctional cleavage sequences (JCS). In some embodiments, the junctional cleavage sequences act to cleave the T7 RNA polymerase or Pol II-encoded RNA transcript at the junction of the viral RNA and the mammalian mRNA sequence such that the non-viral RNA polynucleotides are removed from the transcript in order to maintain the endogenous 5’ and 3’ discrete ends. In some embodiments, the junctional cleavage sequences act to generate the appropriate ends during the linearization of the DNA plasmid encoding the recombinant RNA molecules (e.g., the use of 3’ restriction enzyme recognition sequences to produce the appropriate 3’ end upon linearization of the plasmid template and prior to in vitro transcription of the recombinant RNA molecules). [0230] The nature of the junctional cleavage sequences and the removal of the non- viral RNA from the viral genome transcript can be accomplished by a variety of methods. [0231] For example, in some embodiments, the junctional cleavage sequences are targets for RNA interference (RNAi) molecules. “RNA interference molecule” as used herein refers to an RNA polynucleotide that mediates degradation of a target mRNA sequence through endogenous gene silencing pathways (e.g., Dicer and RNA-induced silencing complex (RISC)). Exemplary RNA interference agents include microRNAs (miRNAs), artificial miRNA (amiRNAs), short hairpin RNAs (shRNAs), and small interfering RNAs (siRNAs). Further, any system for cleaving an RNA transcript at a specific site currently known the art or to be defined in the future can be used to generate the discrete ends of the recombinant RNA molecule. [0232] In some embodiments, the RNAi molecule is a miRNA. In some embodiments, the RNAi molecule is an artificial miRNA (amiRNA) derived from a synthetic miRNA- embedded in a Pol II transcript. In some embodiments, the RNAi molecule is an siRNA molecule. In some embodiments, the junctional cleavage sequences are guide RNA (gRNA) target sequences. In some embodiments, the junctional cleavage sequences are pri-miRNA- encoding sequences. In some embodiments, the junctional cleavage sequences are primer binding sequences that facilitate cleavage by the endoribonuclease, RNAseH. [0233] In some embodiments, the junctional cleavage sequences are restriction enzyme recognition sites (Restr Enz RS) and result in the generation of discrete ends of viral transcripts during linearization of the plasmid template runoff RNA synthesis with T7 RNA Polymerase. In some embodiments, the junctional cleavage sequences are Type IIS restriction enzyme recognition sites. Type IIS restriction enzymes comprise a specific group of enzymes which recognize asymmetric DNA sequences and cleave at a defined distance outside of their recognition sequence, usually within 1 to 20 nucleotides. Exemplary Type IIS restriction enzymes include AcuI, AlwI, BaeI, BbsI, BbvI, BccI, BceAI, BcgI, BciVI, BcoDI, BfuAI, BmrI, BpmI, BpuEI, BsaI, BsaXI, BseRI, BsgI, BsmAI, BsmBi, BsmFI, BsmI, BspCNI, BspMI, BspQI, BsrDI, BsrI, BtgZI, BtsCI, BstI, CaspCI, EarI, EciI, Esp3I, FauI, FokI, HgaI, HphI, HpyAV, MbolI, MlyI, MmeI, MnlL, NmeAIII, PleI, SapI, and SfaNI. The recognition sequences for these Type IIS restriction enzymes are known in the art. See the New England Biolabs website located at neb.com/tools-and-resources/selection-charts/type-iis-restriction- enzymes. [0234] Accordingly, in some embodiments, when the junctional cleavage sequence comprises restriction enzyme recognition sites, the viral genome does not comprise the corresponding RNA polynucleotide sequences. For example, if the junctional cleavage sequence comprise BsaI restriction enzyme recognition site, the viral genome of the RNA virus does not comprise the polynucleotide sequence

(SEQ ID NO: 21) or

(SEQ ID NO: 22), because the corresponding, complementary DNA sequences,

(SEQ ID NO: 23) and

(SEQ ID NO: 24), are BsaI restriction enzyme recognition sites. [0235] In some embodiments, the junctional cleavage sequences are ribozyme- encoding sequences and mediate self-cleavage of the recombinant RNA molecules intermediates to produce the discrete 5’ and 3’ ends of required for the final recombinant RNA molecules and subsequent production of infectious RNA viruses. Exemplary ribozymes include the Hammerhead ribozyme (e.g., the Hammerhead ribozymes), the Varkud satellite (VS) ribozyme, the hairpin ribozyme, the GIR1 branching ribozyme, the glmS ribozyme, the twister ribozyme, the twister sister ribozyme, the pistol ribozyme (e.g., Pistol 1 and Pistol 2), the hatchet ribozyme, and the Hepatitis delta virus ribozyme. In some embodiments, the 5’ and/or 3’ junctional cleavage sequences are ribozyme encoding sequences. [0236] In some embodiments, the junctional cleavage sequences are sequences encoding ligand-inducible self-cleaving ribozymes, referred to as “aptazymes”. Aptazymes are ribozyme sequences that contain an integrated aptamer domain specific for a ligand. Ligand binding to the apatmer domain triggers activation of the enzymatic activity of the ribozyme, thereby resulting in cleavage of the RNA transcript. Exemplary aptazymes include theophylline-dependent aptazymes (e.g., hammerhead ribozyme linked to a theophylline- dependent aptamer), tetracycline-dependent aptazymes (e.g., hammerhead ribozyme linked to a Tet-dependent aptamer), guanine-dependent aptazymes (e.g., hammerhead ribozyme linked to a guanine-dependent aptamer). In some embodiments, the 5’ and/or 3’ junctional cleavage sequences are aptazyme-encoding sequences. [0237] In some embodiments, the 5’ junctional cleavage sequence and 3’ junctional cleavage sequence are from the same group (e.g., are both RNAi target sequences, both ribozyme-encoding sequences, etc.). For example, in some embodiments, the junctional cleavage sequences are RNAi target sequences (e.g., siRNA, shRNA, amiRNA, or miRNA target sequences) and are incorporated into the 5’ and 3’ ends of the polynucleotide encoding the recombinant RNA molecule. In such embodiments, the 5’ and 3’ RNAi target sequence may be the same (i.e., targets for the same siRNA, shRNA, amiRNA, or miRNA) or different (i.e., the 5’ sequence is a target for one siRNA, shRNA, amiRNA, or miRNA and the 3’ sequence is a target for another siRNA, shRNA, amiRNA, or miRNA). In some embodiments, the junctional cleavage sequences are guide RNA target sequences and are incorporated into the 5’ and 3’ ends of the polynucleotide encoding the recombinant RNA molecule. In such embodiments, the 5’ and 3’ gRNA target sequences may be the same (i.e., targets for the same gRNA) or different (i.e., the 5’ sequence is a target for one gRNA and the 3’ sequence is a target for another gRNA). In some embodiments, the junctional cleavage sequences are pri- mRNA-encoding sequences and are incorporated into the 5’ and 3’ ends of the polynucleotide encoding the recombinant RNA molecule. In some embodiments, the junctional cleavage sequences are ribozyme-encoding sequences and are incorporated immediately 5’ and 3’ of the polynucleotide sequence encoding the recombinant RNA molecule. [0238] In some embodiments, the 5’ junctional cleavage sequence and 3’ junctional cleavage sequence are from the same group but are different variants or types. For example, in some embodiments, the 5’ and 3’ junctional cleavage sequences may be target sequences for an RNAi molecule, wherein the 5’ junctional cleavage sequence is an siRNA target sequence and the 3’ junctional cleavage sequence is a miRNA target sequence (or vis versa). In some embodiments, the 5’ and 3’ junctional cleavage sequences may be ribozyme-encoding sequences, wherein the 5’ junctional cleavage sequence is a hammerhead ribozyme-encoding sequence and the 3’ junctional cleavage sequence is a hepatitis delta virus ribozyme-encoding sequence. [0239] In some embodiments, the 5’ junctional cleavage sequence and 3’ junctional cleavage sequence are different types. For example, in some embodiments, the 5’ junctional cleavage sequence is an RNAi target sequence (e.g., an siRNA, an amiRNA, or a miRNA target sequence) and the 3’ junctional cleavage sequence is a ribozyme sequence, an aptazyme sequence, a pri-miRNA sequence, or a gRNA target sequence. In some embodiments, the 5’ junctional cleavage sequence is a ribozyme sequence and the 3’ junctional cleavage sequence is an RNAi target sequence (e.g., an siRNA, an amiRNA, or a miRNA target sequence), an aptazyme sequence, a pri-miRNA-encoding sequence, or a gRNA target sequence. In some embodiments, the 5’ junctional cleavage sequence is an aptazyme sequence and the 3’ junctional cleavage sequence is an RNAi target sequence (e.g., an siRNA, an amiRNA, or a miRNA target sequence), a ribozyme sequence, a pri-miRNA sequence, or a gRNA target sequence. In some embodiments, the 5’ junctional cleavage sequence is a pri-miRNA sequence and the 3’ junctional cleavage sequence is an RNAi target sequence (e.g., an siRNA, an amiRNA, or a miRNA target sequence), a ribozyme sequence, an aptazyme sequence, or a gRNA target sequence. In some embodiments, the 5’ junctional cleavage sequence is a gRNA target sequence and the 3’ junctional cleavage sequence is an RNAi target sequence (e.g., an siRNA, an amiRNA, or a miRNA target sequence), a ribozyme sequence, a pri-miRNA sequence, or an aptazyme sequence. [0240] Exemplary arrangements of the junctional cleavage sequences relative to the polynucleotide encoding the recombinant RNA molecule are shown below in Table 3 and Table 4. Table 3: Symmetrical Junctional Cleavage Sequence (JSC) Arrangements

Table 4: Asymmetrical JCS Arrangements

*“Restr Enz RS” refers to restriction enzyme recognition site Ribozyme Encoding Sequence [0241] In some embodiments, the 5’ junctional cleavage sequence comprises or consists of a ENV27 ribozyme encoding sequence. In some embodiments, the ENV27 ribozyme encoding sequence comprises or consists of a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% (including all ranges and subranges therebetween) sequence identity to any one of SEQ ID NO: 33-37. In some embodiments, the ENV27 ribozyme encoding sequence comprises or consists of a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% (including all ranges and subranges therebetween) sequence identity to SEQ ID NO: 33. [0242] In some embodiments, the ENV27 ribozyme encoding sequence contains modification (e.g., insertion) at the P3 stem insert region, which correspond to nucleotides 49- 54 of SEQ ID NO: 33. Without wishing to be bound by any particular theory, it is hypothesized that extending the P3 stem insert region may facilitate the folding and/or cleavage efficiency of the ENV27 ribozyme. In some embodiments, the ENV27 ribozyme encoding sequence comprises a P3 stem insert of about 1-30, about 1-25, about 1-20, about 1-15, about 1-10, about 5-30, about 5-25, about 5-20, about 5-15, about 5-10, about 6-30, about 6-25, about 6-20, about 6-15, or about 6-10 polynucleotides in length. In some embodiments, the ENV27 ribozyme encoding sequence comprises the P3 stem insert of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 polynucleotides in length. In some embodiments, the P3 stem insert comprises or consists of the polynucleotides “AGATCT” at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33. In some embodiments, the P3 stem insert comprises or consists of the polynucleotides

(SEQ ID NO: 39) at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33. In some embodiments, the P3 stem insert comprises or consists of the polynucleotides

(SEQ ID NO: 40) at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33. [0243] In some embodiments, the ENV27 ribozyme encoding sequence comprises or consists of a sequence (excluding the P3 stem insert region) having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% (including all ranges and subranges therebetween) sequence identity to SEQ ID NO: 33 (excluding its P3 stem insert corresponding to nucleotides 49-54 of SEQ ID NO: 33). In some embodiments, the ENV27 ribozyme encoding sequence comprises or consists of a sequence (excluding the P3 stem insert region) that is 100% identical to SEQ ID NO: 33 (excluding its P3 stem insert corresponding to nucleotides 49-54 of SEQ ID NO: 33). In some embodiments, the ENV27 ribozyme encoding sequence comprises or consists of a sequence (excluding the P3 stem insert region) having at most 1, at most 2, at most 3, at most 5, at most 5, at most 6, at most 7, at most 8, at most 8, at most 10, or at most 11 mutations (insertions, deletions or substitutions) as compared to, SEQ ID NO: 33 (excluding its P3 stem insert corresponding to nucleotides 49-54 of SEQ ID NO: 33). In some embodiments, such mutation(s) are substitution(s). [0244] In some embodiments, the ENV27 ribozyme encoding sequence comprises the polynucleotides

at the positions corresponding to nucleotides 25-30 of SEQ ID NO: 33. [0245] In some embodiments, the ENV27 ribozyme encoding sequence comprises the polynucleotides

at the positions corresponding to nucleotides 25-30 of SEQ ID NO: 33. [0246] In some embodiments, the ENV27 sequence is incorporated into the recombinant DNA molecule for in vitro transcription of a RNA viral genome of the disclosure. Leader Sequence [0247] In some embodiments, the DNA vector that expresses the RNA viral genome / recombinant RNA virus comprises a leader sequence. In some embodiments, the leader sequence is located in between the promoter and the 5’ junctional cleavage sequence (e.g., the ribozyme encoding sequence). [0248] In some embodiments, the leader sequence comprises or consists of a polynucleotide sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% (including all ranges and subranges therebetween) sequence identity according to any one of SEQ ID NO: 32 or 38. In some embodiments, the leader sequence comprises or consists of a polynucleotide sequence according to any one of SEQ ID NO: 32 or 38. In some embodiments, the leader sequence comprises or consists of a polynucleotide sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% (including all ranges and subranges therebetween) sequence identity according to SEQ ID NO: 32. In some embodiments, the leader sequence comprises or consists of a polynucleotide sequence according to SEQ ID NO: 32. In some embodiment, the leader sequence is followed, or immediately followed, by a ENV27 ribozyme sequence (e.g., any one of SEQ ID NO: 33-37 or a variant thereof). In some embodiments, the leader sequence is incorporated into a recombinant DNA molecule (e.g., DNA template) for in vitro transcription of a RNA viral genome of the disclosure. Particles comprising the recombinant RNA molecule [0249] In some embodiments, the recombinant RNA molecules of the disclosure are comprised within particles. In some embodiments, the particle is a virus particle. In some embodiments, the particle is a non-viral particle (e.g., LNP). [0250] In some embodiments, the disclosure provides virus particles comprising the recombinant RNA molecules of the disclosure (e.g., particles of the chimeric virus encoded by the viral genome of the disclosure). In some embodiments, the recombinant RNA molecules of the disclosure are capable of producing virus particles. In some embodiments, the disclosure provides virus particles produced by the recombinant RNA molecules of the disclosure. [0251] In some embodiments, the particle is not a virus particle (i.e., a non-viral particle). In some embodiments, the particle is a non-tissue derived composition of matter such as liposomes, lipoplexes, nanoparticles, nanocapsules, microparticles, microspheres, lipid particles, exosomes, vesicles, and the like. In some embodiments, the particles are non- proteinaceous and non-immunogenic. In such embodiments, encapsulation of the recombinant RNA molecules of the disclosure allows for delivery of a viral genome without the induction of a systemic, anti-viral immune response and mitigates the effects of neutralizing anti-viral antibodies. Further, encapsulation of the recombinant RNA molecules of the disclosure shields the genomes from degradation and facilitates the introduction into target host cells. In some embodiments, the particles are nanoparticles. In some embodiments, the particles are lipid nanoparticles. In some embodiments, the particles are exosomes. [0252] The disclosure provides particles comprising a recombinant RNA molecule of the disclosure. In some embodiments, the particle is a lipid nanoparticle. In some embodiments, the particle comprises no additional nucleic acid molecule other than the recombinant RNA molecule. In some embodiments, the particles comprises no viral protein. [0253] In some embodiments, the particle is biodegradable in a subject. In such embodiments, multiple doses of the particles can be administered to a subject without an accumulation of particles in the subject. Examples of suitable particles include polystyrene particles, poly(lactic-co-glycolic acid) PLGA particles, polypeptide-based cationic polymer particles, cyclodextrin particles, chitosan particles, lipid-based particles, poly(β-amino ester) particles, low-molecular-weight polyethylenimine particles, polyphosphoester particles, disulfide cross-linked polymer particles, polyamidoamine particles, polyethylenimine (PEI) particles, and PLURIONICS stabilized polypropylene sulfide particles. [0254] In some embodiments, the polynucleotides of the disclosure are encapsulated in inorganic particles. In some embodiments, the inorganic particles are gold nanoparticles (GNP), gold nanorods (GNR), magnetic nanoparticles (MNP), magnetic nanotubes (MNT), carbon nanohorns (CNH), carbon fullerenes, carbon nanotubes (CNT), calcium phosphate nanoparticles (CPNP), mesoporous silica nanoparticles (MSN), silica nanotubes (SNT), or a starlike hollow silica nanoparticle (SHNP). [0255] In some embodiments, the particles of the disclosure are nanoscopic in size, in order to enhance solubility, avoid possible complications caused by aggregation in vivo and to facilitate pinocytosis. In some embodiments, the particle has an average diameter of about less than about 1000 nm. In some embodiments, the particle has an average diameter of less than about 500 nm. In some embodiments, the particle has an average diameter of between about 30 and about 100 nm, between about 50 and about 100 nm, or between about 75 and about 100 nm. In some embodiments, the particle has an average diameter of between about 30 and about 75 nm or between about 30 and about 50 nm. In some embodiments, the particle has an average diameter between about 100 and about 500 nm. In some embodiments, the particle has an average diameter between about 200 and 400 nm. In some embodiments, the particle has an average size of about 350 nm. Lipid Nanoparticles [0256] In some embodiments, the recombinant RNA molecules described herein are encapsulated in a lipid nanoparticle (LNP). In certain embodiments, the LNP comprises one or more lipids such as such as triglycerides (e.g., tristearin), diglycerides (e.g., glycerol bahenate), monoglycerides (e.g., glycerol monostearate), fatty acids (e.g., stearic acid), steroids (e.g., cholesterol), and waxes (e.g., cetyl palmitate). In some embodiments, the LNP comprises one or more cationic lipids and one or more helper lipids. In some embodiments, the LNP comprises one or more cationic lipids, a cholesterol, and one or more neutral lipids [0257] Cationic lipids refer to any of a number of lipid species that carry a net positive charge at a selected pH, such as physiological pH. Such lipids include, but are not limited to 1,2-DiLinoleyloxy-N,N-dimethylaminopropane (DLinDMA), 1,2-Dilinolenyloxy-N,N- dimethylaminopropane (DLenDMA), dioctadecyldimethylammonium (DODMA), distearyldimethylammonium (DSDMA), N,N-dioleyl-N,N-dimethylammonium chloride (DODAC); N-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA); N,N- distearyl-N,N-dimethylammonium bromide (DDAB); N-(2,3-dioleoyloxy)propyl)-N,N,N- trimethylammonium chloride (DOTAP); 3-(N — (N ′ ,N ′ -dimethylaminoethane)- carbamoyl)cholesterol (DC-Chol), and N-(1,2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N- hydroxyethyl ammonium bromide (DMRIE). For example, cationic lipids that have a positive charge at below physiological pH include, but are not limited to, DODAP, DODMA, and DMDMA. In some embodiments, the cationic lipids comprise C18 alkyl chains, ether linkages between the head group and alkyl chains, and 0 to 3 double bonds. Such lipids include, e.g., DSDMA, DLinDMA, DLenDMA, and DODMA. The cationic lipids may comprise ether linkages and pH titratable head groups. Such lipids include, e.g., DODMA. [0258] In some embodiments, the cationic lipids comprise a protonatable tertiary amine head group. Such lipids are referred to herein as ionizable lipids. Ionizable lipids refer to lipid species comprising an ionizable amine head group and typically comprising a pKa of less than about 7. Therefore, in environments with an acidic pH, the ionizable amine head group is protonated such that the ionizable lipid preferentially interacts with negatively charged molecules (e.g., nucleic acids such as the recombinant polynucleotides described herein) thus facilitating nanoparticle assembly and encapsulation. Therefore, in some embodiments, ionizable lipids can increase the loading of nucleic acids into lipid nanoparticles. In environments where the pH is greater than about 7 (e.g., physiologic pH of ≈ 7.4), the ionizable lipid comprises a neutral charge. When particles comprising ionizable lipids are taken up into the low pH environment of an endosome (e.g., pH < 7), the ionizable lipid is again protonated and associates with the anionic endosomal membranes, promoting release of the contents encapsulated by the particle. In some embodiments, the LNP comprises an ionizable lipid, e.g., a 7.SS-cleavable and pH-responsive lipid like material (such as the COATSOME® SS-Series). [0259] In some embodiments, the cationic lipid is an ionizable lipid selected from DLinDMA, DLin-KC2-DMA, DLin-MC3-DMA (MC3), COATSOME® SS-LC (former name: SS-18/4PE-13), COATSOME® SS-EC (former name: SS-33/4PE-15), COATSOME® SS-OC, COATSOME® SS-OP, Di((Z)-non-2-en-1-yl)9-((4-dimethylamino)butanoyl)oxy) heptadecanedioate (L-319), or N-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP). In some embodiments, the cationic ionizable lipid is DLin-MC3-DMA (MC3). In some embodiments, the cationic ionizable lipid is COATSOME® SS-LC. In some embodiments, the cationic ionizable lipid is COATSOME® SS-EC. In some embodiments, the cationic ionizable lipid is COATSOME® SS-OC. In some embodiments, the cationic ionizable lipid is COATSOME® SS-OP. In some embodiments, the cationic ionizable lipid is L-319. In some embodiments, the cationic ionizable lipid is DOTAP. [0260] In some embodiments, the LNPs comprise one or more non-cationic helper lipids (neutral lipids). Exemplary neutral helper lipids include (1,2-dilauroyl-sn-glycero-3- phosphoethanolamine) (DLPE), 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DiPPE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), 1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2- dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-dimyristoyl-sn-glycero-3- phosphoethanolamine (DMPE), (1,2-dioleoyl-sn-glycero-3- phospho-(l’-rac-glycerol) (DOPG), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3- phosphoethanolamine (DSPE), ceramides, sphingomyelins, and cholesterol. In some embodiments, the one or more helper lipids are selected from 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC); 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE); 1,2- dioleoyl-sn-glycero-3-phosphocholine (DOPC); 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE); and cholesterol. In some embodiments, the LNPs comprise DSPC. In some embodiments, the LNPs comprise DOPC. In some embodiments, the LNPs comprise DLPE. In some embodiments, the LNPs comprise DOPE. [0261] The use and inclusion of polyethylene glycol (PEG)-modified phospholipids and derivatized lipids such as derivatized ceramides (PEG-CER), including N-octanoyl- sphingosine-l-[succinyl(methoxy polyethylene glycol)-2000] (C8 PEG-2000 ceramide) in the liposomal and pharmaceutical compositions described herein is also contemplated, preferably in combination with one or more of the compounds and lipids disclosed herein. [0262] In some embodiments, the lipid nanoparticles may further comprise one or more of PEG-modified lipids that comprise a poly(ethylene)glycol chain of up to 5kDa in length covalently attached to a lipid comprising one or more C6-C20 alkyls. In some embodiments, the LNPs further comprise 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE-PEG), or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino(polyethylene glycol)] (DSPE-PEG-amine). In some embodiments, the LNPs further comprise a PEG-modified lipid selected from 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-N-[amino(polyethyleneglycol)-5000] (DSPE-PEG5K); 1,2- dipalmitoyl-rac-glycerol methoxypolyethylene glycol-2000 (DPG-PEG2K); 1,2-distearoyl- rac-glycero-3-methylpolyoxyethylene-5000 (DSG-PEG5K); 1,2-distearoyl-rac-glycero-3- methylpolyoxyethylene-2000 (DSG-PEG2K); 1,2-dimyristoyl-rac-glycero-3- methylpolyoxyethylene-5000 (DMG-PEG5K); and 1,2-dimyristoyl-rac-glycero-3- methylpolyoxyethylene-2000 (DMG-PEG2K). In some embodiments, the LNPs further comprise DSPE-PEG5K. In some embodiments, the LNPs further comprise DPG-PEG2K. In some embodiments, the LNPs further comprise DSG-PEG2K. In some embodiments, the LNPs further comprise DMG-PEG2K. In some embodiments, the LNPs further comprise DSG- PEG5K. In some embodiments, the LNPs further comprise DMG-PEG5K. In some embodiments, the PEG-modified lipid comprises about 0.1% to about 1% of the total lipid content in a lipid nanoparticle. In some embodiments, the PEG-modified lipid comprises about 0.1%, about 0.2% about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0 %, about 1.5%, about 2.0%, about 2.5%, or about 3.0% of the total lipid content in the lipid nanoparticle. [0263] In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the cationic lipid is DOTAP. In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the cationic lipid is DLin-MC3-DMA (MC3). In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the cationic lipid is COATSOME® SS-EC. In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the cationic lipid is COATSOME® SS-LC. In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the cationic lipid is COATSOME® SS-OC. In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the cationic lipid is COATSOME® SS-OP. In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the cationic lipid is L-319. [0264] In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the one or more helper lipids comprises cholesterol. In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the one or more helper lipids comprises DLPE. In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the one or more helper lipids comprises DSPC. In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the one or more helper lipids comprises DOPE. In some embodiments, the LNP comprises a cationic lipid and one or more helper lipids, wherein the one or more helper lipids comprises DOPC. [0265] In some embodiments, the LNPs have an average size of about 50 nm to about 500 nm. For example, in some embodiments, the LNPs have an average size of about 50 nm to about 200 nm, about 100 nm to about 200 nm, about 150 nm to about 200 nm, about 50 nm to about 150 nm, about 100 nm to about 150 nm, about 150 nm to about 500 nm, about 200 nm to about 500 nm, about 300 nm to about 500 nm, about 350 nm to about 500 nm, about 400 nm to about 500 nm, about 425 nm to about 500 nm, about 450 nm to about 500 nm, or about 475 nm to about 500 nm. In some embodiments, the plurality of LNPs have an average size of about 50 nm to about 120 nm. In some embodiments, the plurality of LNPs have an average size of about 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, or about 120 nm. In some embodiments, the plurality of LNPs have an average size of about 100 nm. [0266] In some embodiments, the LNPs have a neutral charge (e.g., an average zeta- potential of between about 0 mV and 1 mV). In some embodiments, the LNPs have an average zeta-potential of between about 40 mV and about -40 mV. In some embodiments, the LNPs have an average zeta-potential of between about 40 mV and about 0 mV. In some embodiments, the LNPs have an average zeta-potential of between about 35 mV and about 0 mV, about 30 mV and about 0 mV, about 25 mV to about 0 mV, about 20 mV to about 0 mV, about 15 mV to about 0 mV, about 10 mV to about 0 mV, or about 5 mV to about 0 mV. In some embodiments, the LNPs have an average zeta-potential of between about 20 mV and about -40 mV. In some embodiments, the LNPs have an average zeta-potential of between about 20 mV and about -20 mV. In some embodiments, the LNPs have an average zeta-potential of between about 10 mV and about -20 mV. In some embodiments, the LNPs have an average zeta- potential of between about 10 mV and about -10 mV. In some embodiments, the LNPs have an average zeta-potential of about 10 mV, about 9 mV, about 8 mV, about 7 mV, about 6 mV, about 5 mV, about 4 mV, about 3 mV, about 2 mV, about 1 mV, about 0 mV, about -1 mV, about -2 mV, about -3 mV, about -4 mV, about -5 mV, about -6 mV, about -7 mV, about -8 mV, about -9 mV, about -9 mV or about -10 mV. [0267] In some embodiments, the LNPs have an average zeta-potential of between about 0 mV and -20 mV. In some embodiments, the LNPs have an average zeta-potential of less than about -20 mV. For example, in some embodiments, the LNPs have an average zeta- potential of less than about less than about -30 mV, less than about 35 mV, or less than about -40 mV. In some embodiments, the LNPs have an average zeta-potential of between about -50 mV to about – 20 mV, about -40 mV to about -20 mV, or about -30 mV to about -20 mV. In some embodiments, the LNPs have an average zeta-potential of about 0 mV, about -1 mV, about -2 mV, about -3 mV, about -4 mV, about -5 mV, about -6 mV, about -7 mV, about -8 mV, about -9 mV, about -10 mV, about -11 mV, about -12 mV, about -13 mV, about -14 mV, about -15 mV, about -16 mV, about -17 mV, about -18 mV, about -19 mV, about -20 mV, about -21 mV, about -22 mV, about -23 mV, about -24 mV, about -25 mV, about -26 mV, about -27 mV, about -28 mV, about -29 mV, about -30 mV, about -31 mV, about -32 mV, about -33 mV, about -34 mV, about -35 mV, about -36 mV, about -37 mV, about -38 mV, about -39 mV, or about -40 mV. [0268] In some embodiments, the lipid nanoparticles comprise a recombinant nucleic acid molecule described herein and comprise a ratio of lipid (L) to nucleic acid (N) of about 3:1 (L:N). In some embodiments, the lipid nanoparticles comprise a recombinant nucleic acid molecule described herein and comprise an L:N ratio about 4:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, or about 10:1. In some embodiments, the lipid nanoparticles comprise a recombinant nucleic acid molecule described herein and comprise a ratio of lipid (L) to nucleic acid (N) of about 7:1. In some embodiments, the lipid nanoparticles comprise a recombinant nucleic acid molecule described herein and comprise an L:N ratio about 4.5:1, about 4.6:1, about 4.7:1, about 4.8:1, about 4.9:1, about 5:1, about 5.1:1, about 5.2:1, about 5.3:1, about 5.4:1, or about 5.5:1. In some embodiments, the lipid nanoparticles comprise a recombinant nucleic acid molecule described herein and comprise an L:N ratio about 6.5:1, 6.6:1, 6.7:1, 6.8:1, 6.9:1, 7:1, 7.1:1, 7.2:1, 7.3:1, 7.4:1, and 7.5:1. Cationic Lipid Compounds of Formula (I) [0269] In some embodiments, the lipid nanoparticle comprises a cationic lipid of Formula (I):

, Formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein: A is –N(CH₂R^N1)(CH₂R^N2) or a 4-7-membered heterocyclyl ring containing at least one N, wherein the 4-7-membered heterocyclyl ring is optionally substituted with 0-6 R³; each X is independently

R¹ is selected from the group consisting of optionally substituted C₁-C₃₁ aliphatic and steroidyl; R² is selected from the group consisting of optionally substituted C₁-C₃₁ aliphatic and steroidyl; R³ is optionally substituted C₁-C₆ aliphatic; R^N1 and R^N2 are each independently hydrogen, hydroxy-C₁-C₆ alkyl, C₂-C₆ alkenyl, or a C₃-C₇ cycloalkyl; L¹ is selected from the group consisting of an optionally substituted C₁-C₂₀ alkylene chain and a bivalent optionally substituted C₂-C₂₀ alkenylene chain; L² is selected from the group consisting of an optionally substituted C₁-C₂₀ alkylene chain and a bivalent optionally substituted C₂-C₂₀ alkenylene chain; L³ is a bond, an optionally substituted C₁-C₆ alkylene chain, or a bivalent optionally substituted C₃-C₇ cycloalkylene. [0270] In some embodiments, when A is –N(CH₃)(CH₃) and X is O, L³ is not a C₁-C₆ alkylene chain. [0271] In some embodiments, the present disclosure includes a compound of Formula (I-a):

, Formula (I-a) or a pharmaceutically acceptable salt or solvate thereof, wherein m is 0, 1, 2, 3, 4, 5, or 6. [0272] In some embodiments, the present disclosure includes a compound of Formula (I-b):

, Formula (I-b) or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, 2, or 3; and m is 0, 1, 2, 3, 4, 5, or 6. [0273] In some embodiments, the present disclosure includes a compound of Formula (I-bi):

, Formula (I-bi) or a pharmaceutically acceptable salt or solvate thereof. [0274] In some embodiments, the present disclosure includes a compound of Formula (I-bii):

, Formula (I-bii) or a pharmaceutically acceptable salt or solvate thereof, wherein m is 0, 1, 2, or 3; and p and q are each 0, 1, 2, or 3, and wherein q + p is less than or equal to 3. [0275] In some embodiments, the present disclosure includes a compound of Formula (I-biii):

, Formula (I-biii) or a pharmaceutically acceptable salt or solvate thereof. [0276] In some embodiments, the present disclosure includes a compound of Formula (I-c):

, Formula (I-c) or a pharmaceutically acceptable salt or solvate thereof. [0277] In some embodiments, A is –N(CH₂R^N1)(CH₂R^N2) or an optionally substituted 4-7-membered heterocyclyl ring containing at least one N. [0278] In some embodiments, A is –N(CH₂R^N1)(CH₂R^N2). In some embodiments, R^N1 and R^N2 are each independently selected from hydrogen, hydroxy-C₁-C₃ alkylene, C₂-C₄ alkenyl, or C₃-C₄ cycloalkyl. ). [0279] In some embodiments, R^N1 and R^N2 are each independently selected from hydrogen, –CH₂CH=CH₂, –CH₂CH₂OH,

. In some embodiments, R^N1 and R^N2 are the same. In some embodiments, R^N1 and R^N2 are each hydrogen. In some embodiments, R^N1 and R^N2 are each C₂-C₄ alkenyl, e.g., –CH₂CH=CH₂. In some embodiments, R^N1 and R^N2 are each hydroxy-C₁-C₃ alkylene, e.g., –CH₂CH₂OH. In some embodiments, R^N1 and R^N2 are different. In some embodiments, one of R^N1 and R^N2 is hydrogen and the other one is C₃-C₄ cycloalkyl. In some embodiments, one of R^N1 and R^N2 is hydrogen and the other one

[0280] In some embodiments, A is an optionally substituted 4-7-membered heterocyclyl ring containing at least one N. In some embodiments, A is an optionally substituted 4-7-membered heterocyclyl ring containing exactly one N. In some embodiments, A is an unsubstituted 4-7-membered heterocyclyl ring containing at least one N. In some embodiments, A is unsubstituted 4-7-membered heterocyclyl ring containing exactly one N. In some embodiments, A is an optionally substituted 5-6-membered heterocyclyl ring containing at least one N. In some embodiments, A is unsubstituted 5-6-membered heterocyclyl ring containing at least one N. [0281] In some embodiments, A is an optionally substituted 4-7-membered heterocyclyl ring containing at least one N, and the N atom of A is a tertiary amine. [0282] In some embodiments, A is an optionally substituted 4-7-membered heterocyclyl ring containing at least one N, further containing one or more S. In some embodiments, A is an optionally substituted 4-7-membered heterocyclyl ring containing at least one N, further containing exactly one S. [0283] In some embodiments, A is selected from the group consisting of azetidine, pyrrolidine, piperidine, azepane, and thiomorpholine. In some embodiments, A is selected from the group consisting of pyrrolidine and piperidine. [0284] In some embodiments, L¹ is selected from the group consisting of an optionally substituted C₁-C₂₀ alkylene chain and a bivalent optionally substituted C₁-C₂₀ alkenylene chain. In some embodiments, L² is selected from the group consisting of an optionally substituted C₁- C₂₀ alkylene chain and a bivalent optionally substituted C₁-C₂₀ alkenylene chain. In some embodiments, L¹ is an optionally substituted C₁-C₂₀ alkylene chain. In some embodiments, L² is an optionally substituted C₁-C₂₀ alkylene chain. [0285] In some embodiments, L¹ and L² are the same. In some embodiments, L¹ and L² are different. [0286] In some embodiments, L¹ is an optionally substituted C₁-C₁₀ alkylene chain. In some embodiments, L² is an optionally substituted C₁-C₁₀ alkylene chain. In some embodiments, L¹ is an optionally substituted C₁-C₅ alkylene chain. In some embodiments, L² is an optionally substituted C₁-C₅ alkylene chain. [0287] In some embodiments, L¹ and L² are each -CH₂CH₂CH₂CH₂-. In some embodiments, L¹ and L² are each -CH₂CH₂CH₂-. In some embodiments, L¹ and L² are each - CH₂CH₂-. [0288] In some embodiments, L³ is a bond, an optionally substituted C₁-C₆ alkylene chain, or a bivalent optionally substituted C₃-C₆ cycloalkylene. In some embodiments, L³ is a bond. In some embodiments, L³ is an optionally substituted C₁-C₆ alkylene chain. In some embodiments, L³ is an optionally substituted C₁-C₃ alkylene chain. In some embodiments, L³ is an unsubstituted C₁-C₃ alkylene chain. In some embodiments, L³ is -CH₂-. In some embodiments, L³ is -CH₂CH₂-. In some embodiments, L³ is -CH₂CH₂CH₂-. In some embodiments, L³ is a bivalent C₃-C₆ cyclcoalkylene. In some embodiments, L³ is

. [0289] In some embodiments, the number of carbon atoms between the S of the thiolate of Formula (I) and the N of A is 2-10. In some embodiments, the number of carbon atoms between the S of the thiolate of Formula (I) and the N of A is 2-8. In some embodiments, the number of carbon atoms between the S of the thiolate of Formula (I) and the N of A is 2-5. In some embodiments, the number of carbon atoms between the S of the thiolate of Formula (I) and the N of A is 2-4. In some embodiments, the number of carbon atoms between the S of the thiolate of Formula (I) and the N of A is 2. In some embodiments, the number of carbon atoms between the S of the thiolate of Formula (I) and the N of A is 3. In some embodiments, the number of carbon atoms between the S of the thiolate of Formula (I) and the N of A is 4. [0290] In some embodiments, R¹ is selected from the group consisting of optionally substituted C₁-C₃₁ aliphatic and optionally substituted steroidyl. In some embodiments, R² is selected from the group consisting of optionally substituted C₁-C₃₁ aliphatic and optionally substituted steroidyl. In some embodiments, R¹ is optionally substituted C₁-C₃₁ alkyl. In some embodiments, R² is optionally substituted C₁-C₃₁ alkyl. In some embodiments, R¹ is optionally substituted C₅-C₂₅ alkyl. In some embodiments, R² is optionally substituted C₅-C₂₅ alkyl. In some embodiments, R¹ is optionally substituted C₁₀-C₂₀ alkyl. In some embodiments, R² is optionally substituted C₁₀-C₂₀ alkyl. In some embodiments, R¹ is optionally substituted C₁₀- C20 alkyl. In some embodiments, R² is optionally substituted C10-C20 alkyl. In some embodiments, R¹ is unsubstituted C₁₀-C₂₀ alkyl. In some embodiments, R² is unsubstituted C₁₀-C₂₀ alkyl. [0291] In some embodiments, R¹ is optionally substituted C₁₄-C₁₆ alkyl. In some embodiments, R² is optionally substituted C₁₄-C₁₆ alkyl. In some embodiments, R¹ is unsubstituted C₁₄-C₁₆ alkyl. In some embodiments, R² is unsubstituted C₁₄-C₁₆ alkyl. [0292] In some embodiments, R¹ is optionally substituted branched C₃-C₃₁ alkyl. In some embodiments, R² is optionally substituted branched C₃-C₃₁ alkyl. In some embodiments, R¹ is optionally substituted branched C₁₀-C₂₀ alkyl. In some embodiments, R² is optionally substituted branched C₁₀-C₂₀ alkyl. In some embodiments, R¹ is optionally substituted branched C₁₄-C₁₆ alkyl. In some embodiments, R² is optionally substituted branched C₁₄-C₁₆ alkyl. In some embodiments, R¹ is substituted branched C₃-C₃₁ alkyl. In some embodiments, R² is substituted branched C₃-C₃₁ alkyl. In some embodiments, R¹ is substituted branched C₁₀- C₂₀ alkyl. In some embodiments, R² is substituted branched C₁₀-C₂₀ alkyl. In some embodiments, R¹ is substituted branched C₁₄-C₁₆ alkyl. In some embodiments, R² is substituted branched C₁₄-C₁₆ alkyl. [0293] In some embodiments, R¹ and R² are the same. [0294] In some embodiments, R¹ and R² are different. In some embodiments, R¹ is optionally substituted C₆-C₂₀ alkenyl and R² is optionally substituted C₁₀-C₂₀ alkyl. In some embodiments, R¹ is C₆-C₂₀ alkenyl and R² is branched C₁₀-C₂₀ alkyl. [0295] In some embodiments, A is 4-7-membered heterocyclyl ring containing at least one N and optionally substituted with 0-6 R³. In some embodiments, R³ is optionally substituted C₁-C₆ aliphatic. In some embodiments, R³ is optionally substituted C₁-C₃ aliphatic. In some embodiments, R³ is optionally substituted C₁-C₆ alkyl. In some embodiments, R³ is optionally substituted C₁-C₃ alkyl. In some embodiments, R³ is unsubstituted C₁-C₆ alkyl. In some embodiments, R³ is unsubstituted C₁-C₃ alkyl. In some embodiments, R³ is optionally substituted C₁-C₆ alkenyl. In some embodiments, R³ is optionally substituted C₁-C₃ alkenyl. In some embodiments, R³ is unsubstituted C₁-C₆ alkenyl. In some embodiments, R³ is unsubstituted C₁-C₃ alkenyl. [0296] In some embodiments, R³ is substitute with 1-3 C₃-C₆ cycloalkyl. In some embodiments, R³ is substitute with 1 C₃-C₆ cycloalkyl. In some embodiments, R³ is substitute with a cyclopropanyl. In some embodiments, R³ is substitute with 1-3 –OH. In some embodiments, R³ is substitute with 1 –OH. [0297] In some embodiments, m is 0, 1, 2, 3, 4, 5, or 6. In some embodiments m is 0 or 1. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. In some embodiments, m is 5. In some embodiments, m is 6. [0298] In some embodiments, n is 0, 1, 2, or 3. In some embodiments n is 1 or 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. [0299] In some embodiments, a compound of Formula (I) is a compound selected from Table 5, or a pharmaceutically acceptable salt or solvate thereof. Table 5. Selective Examples of The Compound of Formula (I)

Compounds of Formula (II) [0300] In some embodiments, the cationic lipid of the LNP is a compound of Formula (II-1):

Formula (II-1), or a pharmaceutically acceptable salt or solvate thereof, wherein: R^la and R^1b are each independently C₁-C₈ aliphatic or –O(C₁-C₈ aliphatic)–, wherein the O atom, when present, is bonded to the piperidine ring; X^a and X^b are each independently –C(O)O–*, –OC(O)–*, –C(O)N(R_x ¹)–*, – N(R_x ¹)C(O)–*, –O(C=O)N(R_x ¹)–*, –N(R_x ¹)(C=O)O–*, or –O–, wherein –* indicates the attachment point to R^2a or R^2b, respectively and wherein each occurrence of R_x ¹ is independently selected from hydrogen and optionally substituted C₁-C₄ alkyl; and R^2a and R^2b are each independently a sterol residue, a liposoluble vitamin residue, or an C₁₃-C₂₃ aliphatic. [0301] In some embodiments, the cationic lipid of the LNP is a compound of Formula (II-2):

Formula (II-2), or a pharmaceutically acceptable salt or solvate thereof, wherein: R^1a’ and R^1b’ are each independently C₁-C₈ alkylene or –O(C₁-C₈ alkylene), wherein the O atom, when present, is bonded to the piperidine ring; Y^a’ and Y^b’ are each independently –C(O)O–*, –OC(O)–*, –C(O)N(R_x ¹)–*, – N(R_x ¹)C(O)–*, –O(C=O)N(R_x ¹)–*, –N(R_x ¹)(C=O)O–*, –N(R_x ¹)C(O)N(R_x ¹)–, or –O–, wherein –* indicates the attachment point to R^2a or R^2b, and wherein each occurrence of R_x ¹ is independently selected from hydrogen and optionally substituted C₁-C₄ alkyl; Z^a’ and Z^b’ are each independently optionally substituted arylene–C₀-C₈ alkylene or optionally substituted arylene–C₀-C₈ heteroalkylene, wherein the alkylene or heteroalkylene group is bonded to Y^a’ and Y^b’ , respectively; R^2a’ and R^2b’ are each independently a sterol residue, a liposoluble vitamin residue, or an C₁₂-C₂₂ aliphatic. [0302] In some embodiments, the cationic lipid of the LNP is a compound of Formula (II-1a) (COATSOME® SS-OC) or Formula (II-2a) (COATSOME® SS-OP):

Formula (II-1a)

Formula (II-2a) [0303] In some embodiments, the cationic lipid of the LNP is a compound of Formula (II-1a) (COATSOME® SS-OC). COATSOME® SS-OC is also known as SS-18/4PE-16. [0304] In some embodiments, the cationic lipid of the LNP is a compound of Formula (II-2a) (COATSOME® SS-OP). [0305] In some embodiments, the cationic lipid of the LNP is 1,2-dioleoyl-3- trimethylammonium-propane (DOTAP). Polyethyleneglycol (PEG)-Lipid [0306] In some embodiments, the lipid nanoparticle comprises a PEG-lipid. In some embodiments, the PEG-lipid of the disclosure comprises a hydrophilic head group and a hydrophobic lipid tail. In some embodiments, the hydrophilic head group is a PEG moiety. In some embodiments, PEG-lipid of the disclosure comprises a mono lipid tail. In some embodiments, PEG-lipid of the disclosure comprises a mono alkyl lipid tail, a mono alkenyl lipid tail, a mono alkynyl lipid tail, or a mono acyl lipid tail. In some embodiments, the mono lipid tail comprises an ether group, a carbonyl group, or an ester group. In some embodiments, the PEG-lipid of the disclosure may contain a polyoxyethylene alkyl ether, a polyoxyethylene alkenyl ether, or a polyoxyethylene alkynyl ether (such molecules are also known as BRIJ™ or Brij molecules). In some embodiments, the PEG-lipid of the disclosure may contain a polyoxyethylene alkyl ester, a polyoxyethylene alkenyl ester, or a polyoxyethylene alkynyl ester (such molecules are also known as MYRJ™ molecules). [0307] In some embodiments, the PEG-lipid may contain di-acyl lipid tails. [0308] In some embodiments, the PEG-lipid is a compound of Formula (A)

, Formula (A) or a pharmaceutically acceptable salt or solvate thereof, wherein the variables are defined herein. [0309] In some embodiments, the PEG-lipid is a compound of Formula (A′):

, Formula (A′) or a pharmaceutically acceptable salt thereof, wherein: n is an integer between 10 to 200, inclusive of all endpoints; L^P1’ is a bond, –C(O)–, –[(CH₂)_0-3–C(O)O]_1-3–, –(CH₂)_0-3–C(O)O–(CH₂)_1-3– OC(O)–, or –C(O)N(H)–; R^P1’ is C₅-C₂₅ alkyl or C₅-C₂₅ alkenyl; and R^P2’ is hydrogen or –CH₃. [0310] In some embodiments, L^P1’ is a bond, –C(O)–, –CH₂C(O)O–,–CH₂CH₂C(O)O– , –CH₂C(O)OCH₂C(O)O–, –CH₂C(O)OCH₂CH₂OC(O)–, or –C(O)N(H)–. In some embodiments, R^P1’ is R^P1. In some embodiments, R^P2’ is R^P2. [0311] In some embodiments, the PEG-lipid is a compound of Formula (A′’):

, Formula (A′′) or a pharmaceutically acceptable salt thereof, wherein: n is an integer between 10 to 200, inclusive of all endpoints; L^P1′’ is a bond, –[(CH₂)_0-3–C(O)O]_1-3–, –(CH₂)_0-3–C(O)O–(CH₂)_1-3–OC(O)–, or –C(O)N(H)–; R^P1′’ is C₅-C₂₅ alkyl or C₅-C₂₅ alkenyl; and R^P2′’ is hydrogen or –CH₃. [0312] In some embodiments, L^P1′’ is a bond, –CH₂C(O)O–,–CH₂CH₂C(O)O–, – CH₂C(O)OCH₂C(O)O–, –CH₂C(O)OCH₂CH₂OC(O)–, or –C(O)N(H)–. [0313] In some embodiments, the PEG-lipid is a compound of Formula (A′′-a), Formula (A′′-b), Formula (A′′-c), Formula (A′′-cd), Formula (A′′-e), or Formula (A′′-f):

Formula (A′′-a) Formula (A′′-b)

Formula (A′′-c) Formula (A′′-d)

Formula (A′′-e) Formula (A′′-f) or a pharmaceutically acceptable salt thereof. [0314] In some embodiments, R^P1′’ is R^P1. In some embodiments, R^P2′’ is R^P2. [0315] In some embodiments, the PEG-lipid is a compound of Formula (A′′-f1):

, Formula (A′′-f1) or a pharmaceutically acceptable salt thereof. [0316] In some embodiments, the PEG-lipid is a compound of Formula (A′′-f2):

, Formula (A′′-f2) or a pharmaceutically acceptable salt thereof. [0317] In some embodiments, the PEG-lipid is a compound of Formula (A′′-f3):

Formula (A′′-f3) or a pharmaceutically acceptable salt thereof. [0318] In some embodiments, a PEG-lipid of the disclosure is a compound of Formula (B):

_, Formula (B) or a pharmaceutically acceptable salt thereof, wherein: n is an integer between 10 to 200, inclusive of all endpoints; and R^B1 is C₅-C₂₅ alkyl or C₅-C₂₅ alkenyl. [0319] In some embodiments, R^B1 is R^P1. [0320] In some embodiments, the PEG-lipid is a compound of Formula (B-a):

Formula (B-a), or a pharmaceutically acceptable salt thereof. [0321] In some embodiments, the PEG-lipid is a compound of Formula (B-b):

Formula (B-b), or a pharmaceutically acceptable salt thereof. [0322] In some embodiments, n is, on average, 10 to 200, 10 to 180, 10 to 160, 10 to 140, 10 to 120, 10 to 100, 10 to 80, 10 to 60, 10 to 40, 10 to 20, 20 to 200, 20 to 180, 20 to 160, 20 to 140, 20 to 120, 20 to 100, 20 to 80, 20 to 60, 20 to 40, 40 to 200, 40 to 180, 40 to 160, 40 to 140, 40 to 120, 40 to 100, 40 to 80, 40 to 60, 60 to 200, 60 to 180, 60 to 160, 60 to 140, 60 to 120, 60 to 100, 60 to 80, 80 to 200, 80 to 180, 80 to 160, 80 to 140, 80 to 120, 80 to 100, 100 to 200, 100 to 180, 100 to 160, 100 to 140, 100 to 120, 120 to 200, 120 to 180, 120 to 160, 120 to 140, 140 to 200, 140 to 180, 140 to 160, 160 to 200, 160 to 180, or 180 to 200. In some embodiments, n is, on average, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200. In some embodiments, n is on average about 20. In some embodiments, n is on average about 40. In some embodiments, n is on average about 45. In some embodiments, n is on average about 50. In some embodiments, n is on average about 68. In some embodiments, n is on average about 75. In some embodiments, n is on average about 100. [0323] In some embodiments, the PEG-lipid comprises a PEG moiety having an average molecular weight of about 500 to about 10,000 daltons. In some embodiments, the PEG-lipid comprises a PEG moiety having an average molecular weight of about 500 to about 5,000 daltons, about 500 to about 4,000 daltons, about 500 to about 3,000 daltons, about 500 to about 2,000 daltons, about 500 to about 1,000 daltons, about 500 to about 800 daltons, about 500 to about 600 daltons, about 600 to about 5,000 daltons, about 600 to about 4,000 daltons, about 600 to about 3,000 daltons, about 600 to about 2,000 daltons, about 600 to about 1,000 daltons, about 600 to about 800 daltons, about 800 to about 5,000 daltons, about 800 to about 4,000 daltons, about 800 to about 3,000 daltons, about 800 to about 2,000 daltons, about 800 to about 1,000 daltons, about 1,000 to about 5,000 daltons, about 1,000 to about 4,000 daltons, about 1,000 to about 3,000 daltons, about 1,000 to about 2,000 daltons, about 2,000 to about 5,000 daltons, about 2,000 to about 4,000 daltons, about 2,000 to about 3,000 daltons, about 3,000 to about 5,000 daltons, about 3,000 to about 4,000 daltons, about 5,000 to about 10,000 daltons, about 5,000 to about 7,500 daltons, or about 7,500 to about 10,000 daltons. In some embodiments, the PEG moiety of the PEG-lipid has an average molecular weight of about 1,500 to about 2,500 daltons. In some embodiments, the PEG moiety of the PEG-lipid has an average molecular weight of about 1,000 to about 5,000 daltons. In some embodiments, the PEG-lipid comprises a PEG moiety having an average molecular weight of about 500, about 600, about 800, about 1,000, about 1,500, about 2,000, about ,2500, about 3,000, about 3,500, about 4,000, about 4,500, about 5,000, about 6,000, about 7,000, about 8,000, about 9,000, or about 10,000 daltons. In some embodiments, the PEG-lipid comprises a PEG moiety having an average molecular weight of at least 500, at least 1,000, at least 1,500, at least 2,000, at least 2,500, at least 3,000, at least 3,500, at least 4,000, at least 4,500, at least 5,000, at least 6,000, at least 7,000, at least 8,000, at least 9,000, or at least 10,000 daltons. In some embodiments, the PEG-lipid comprises a PEG moiety having an average molecular weight of no more than 500, no more than 1,000, no more than 1,500, no more than 2,000, no more than 2,500, no more than 3,000, no more than 3,500, no more than 4,000, no more than 4,500, no more than 5,000, no more than 6,000, no more than 7,000, no more than 8,000, no more than 9,000, or no more than 10,000 daltons. All values are inclusive of all endpoints. [0324] In some embodiments, the PEG-lipid is polyoxyethylene (100) stearyl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (20) oleyl ether, polyoxyethylene (20) stearyl ether, or a mixture thereof. In some embodiments, the PEG-lipid is polyoxyethylene (100) stearate, polyoxyethylene (50) stearate, polyoxyethylene (40) stearate, polyoxyethylene palmitate, or a mixture thereof. [0325] In some embodiments of the disclosure, the PEG-lipid is

(BRIJ™ S100), having a CAS number of 9005-00, a linear formula of C₁₈H₃₇(OCH₂CH₂)_nOH wherein n is 100. BRIJ™ S100 is also known, generically, as polyoxyethylene (100) stearyl ether. Accordingly, in some embodiments, the PEG-lipid is HO-PEG100-CH₂(CH₂)₁₆CH₃. [0326] In some embodiments of the disclosure, the PEG-lipid is

(BRIJ™ C20), having a CAS number of 9004-95-9, a linear formula of C₁₆H₃₃(OCH₂CH₂)_nOH wherein n is 20. BRIJ™ C20 is also known as BRIJ™ 58, and, generically, as polyethylene glycol hexadecyl ether, polyoxyethylene (20) cetyl ether. Accordingly, in some embodiments, the PEG-lipid is HO-PEG20-CH₂(CH₂)₁₄CH₃. [0327] In some embodiments of the disclosure, the PEG-lipid is

(BRIJ™ O20), having a CAS number of 9004-98-2, a linear formula of C₁₈H₃₅(OCH₂CH₂)_nOH wherein n is 20. BRIJ™ O20 is also known, generically, as polyoxyethylene (20) oleyl ether. Accordingly, in some embodiments, the PEG-lipid is HO-PEG20-C₁₈H₃₅. [0328] In some embodiments of the disclosure, the PEG-lipid is

(BRIJ™ S20), having a CAS number of 9005-00-9, a linear formula of C₁₈H₃₇(OCH₂CH₂)_nOH wherein n is 20. BRIJ™ S20 is also known, generically, as polyethylene glycol octadecyl ether or polyoxyethylene (20) stearyl ether. Accordingly, in some embodiments, the PEG-lipid is HO-PEG20-CH₂(CH₂)₁₆CH_3. [0329] In some embodiments of the disclosure, the PEG-lipid is

(MYRJ™ S100), having a CAS number of 9004-99-3, a linear formula of C₁₇H₃₅C(O)(OCH₂CH₂)_nOH wherein n is 100. MYRJ™ S100 is also known, generically, as polyoxyethylene (100) stearate. Accordingly, in some embodiments, the PEG- lipid is HO-PEG100-CH₂(CH₂)₁₅CH₃. [0330] In some embodiments of the disclosure, the PEG-lipid is

(MYRJ™ S50), having a CAS number of 9004-99-3, a linear formula of C₁₇H₃₅C(O)(OCH₂CH₂)_nOH wherein n is 50. MYRJ™ S50 is also known, generically, as polyoxyethylene (50) stearate. Accordingly, in some embodiments, the PEG- lipid is HO-PEG50-CH₂(CH₂)₁₅CH₃. [0331] In some embodiments of the disclosure, the PEG-lipid is

(MYRJ™ S40), having a CAS number of 9004-99-3, a linear formula of C₁₇H₃₅C(O)(OCH₂CH₂)_nOH wherein n is 40. MYRJ™ S40 is also known, generically, as polyoxyethylene (40) stearate. Accordingly, in some embodiments, the PEG- lipid is HO-PEG40-CH₂(CH₂)₁₅CH₃. [0332] In some embodiments of the disclosure, the PEG-lipid is

(PEG2k-DMG), having a CAS number of 1607430-62-04, a linear formula of C122H242O50. PEG2k-DMG is also known as 1,2- dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000. [0333] In some embodiments of the disclosure, the PEG-lipid is:

(PEG2k-DPG), having an alkyl composition of R₁COO= C16:0, R₂COO= C16:0. PEG2k-DPG is also known, generically, as 1,2-Dipalmitoyl-rac-glycero-3- methylpolyoxyethylene. [0334] In some embodiments of the disclosure, the PEG-lipid may be PEG- dilauroylglycerol, PEG-dimyristoylglycerol (PEG-DMG), PEG-dipalmitoylglycerol, PEG- distearoylglycerol (PEG-DSPE), PEG-dilaurylglycamide, PEG-dimyristylglycamide, PEG- dipalmitoylglycamide, PEG-distearoylglycamide, PEG-cholesterol (l-[8'-(Cholest-5-en- 3[beta]-oxy)carboxamido-3',6'-dioxaoctanyl]carbamoyl-[omega]-methyl-poly(ethylene glycol), PEG-DMB (3,4-ditetradecoxylbenzyl-[omega]-methyl-poly(ethylene glycol)ether), l,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PEG2k-DMG), l,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PEG2k-DSPE), 1,2-distearoyl-snglycerol, methoxypolyethylene glycol (PEG2k-DSG), poly(ethylene glycol)-2000-dimethacrylate (PEG2k-DMA), or l,2- distearyloxypropyl-3-amine-N-[methoxy(polyethylene glycol)-2000] (PEG2k-DSA). In some embodiments, the PEG-lipid may be PEG2k-DMG. In some embodiments, the PEG-lipid may be PEG2k-DSG. In other embodiments, the PEG-lipid may be PEG2k-DSPE. In some embodiments, the PEG-lipid may be PEG2k-DMA. In yet other embodiments, the PEG-lipid may be PEG2k-C-DMA. In some embodiments, the PEG-lipid may be PEG2k-DSA. In other embodiments, the PEG-lipid may be PEG2k-C11. In some embodiments, the PEG-lipid may be PEG2k-C14. In some embodiments, the PEG-lipid may be PEG2k-C16. In some embodiments, the PEG-lipid may be PEG2k-C18. [0335] In some embodiments, a PEG-lipid having single lipid tail of the disclosure (e.g., PEG-lipid of Formula (A), (A′), (A′′), or (B)) may reduce accelerated blood clearance (ABC) upon administration and/or repeat administration of an LNP composition of the disclosure. In some embodiments, a PEG-lipid having single lipid tail of the disclosure may reduce or deplete PEG-specific antibodies (e.g., anti-PEG IgM) generated by a subject’s immune system upon administration and/or repeat administration of an LNP composition of the disclosure. [0336] In some embodiments, the PEG-lipid comprises a poly(ethylene)glycol chain of up to 5kDa in length covalently attached to a lipid comprising one or more C6-C20 alkyls. In some embodiments, the PEG-lipid is 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine- Poly(ethylene glycol) (DSPE-PEG), or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino(polyethylene glycol)] (DSPE-PEG-amine). In some embodiments, the PEG-lipid is selected from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino(polyethyleneglycol)-5000] (DSPE-PEG5K); 1,2-dipalmitoyl-rac-glycerol methoxypolyethylene glycol-2000 (DPG-PEG2K); 1,2-distearoyl-rac-glycero-3- methylpolyoxyethylene-5000 (DSG-PEG5K); 1,2-distearoyl-rac-glycero-3- methylpolyoxyethylene-2000 (DSG-PEG2K); 1,2-dimyristoyl-rac-glycero-3- methylpolyoxyethylene-5000 (DMG-PEG5K); and 1,2-dimyristoyl-rac-glycero-3- methylpolyoxyethylene-2000 (DMG-PEG2K). In some embodiments, the PEG-lipid is DSPE- PEG5K. In some embodiments, the PEG-lipid is DPG-PEG2K. In some embodiments, the PEG-lipid is DSG-PEG2K. In some embodiments, the PEG-lipid is DMG-PEG2K. In some embodiments, the PEG-lipid is DSG-PEG5K. In some embodiments, the PEG-lipid is DMG- PEG5K. [0337] In some embodiments, the PEG lipid is a cleavable PEG lipid. Examples of PEG derivatives with cleavable bonds include those modified with peptide bonds (Kulkarni et al. (2014). Mmp-9 responsive PEG cleavable nanovesicles for efficient delivery of chemotherapeutics to pancreatic cancer. Mol Pharmaceutics 11:2390–9; Lin et al. (2015). Drug/dye-loaded, multifunctional peg-chitosan-iron oxide nanocomposites for methotraxate synergistically self-targeted cancer therapy and dual model imaging. ACS Appl Mater Interfaces 7:11908–20.), disulfide keys (Yan et al (2014). A method to accelerate the gelation of disulfide-crosslinked hydrogels. Chin J Polym Sci 33:118–27; Wu & Yan (2015). Copper nanopowder catalyzed cross-coupling of diaryl disulfides with aryl iodides in PEG-400. Synlett 26:537–42), vinyl ether bonds, hydrazone bonds (Kelly et al. (2016). Polymeric prodrug combination to exploit the therapeutic potential of antimicrobial peptides against cancer cells. Org Biomol Chem 14:9278–86.), and ester bonds (Xu et al. (2008). Esterase-catalyzed dePEGylation of pH-sensitive vesicles modified with cleavable PEG-lipid derivatives. J Control Release 130:238–45). See also, Fang et al., (2017) Cleaveable PEGylation: a strategy for overcoming the “PEG dilemma” in efficient drug delivery. Drug Delivery 24:2, 22-32. [0338] In some embodiments, the PEG lipid is an activated PEG lipid. Exemplary activated PEG lipids include PEG-NH2, PEG-MAL, PEG-NHS, and PEG-ALD. Such functionalized PEG lipids are useful in the conjugation of targeting moieties to lipid nanoparticles to direct the particles to a particular target cell or tissue (e.g., by the attachment of antigen-binding molecules, peptides, glycans, etc.). In some embodiments, the functionalized moiety (e.g., -NH2, _MAL, -NHS, -ALD) is added to the free end of the PEG moiety of the PEG-lipid of the disclosure (e.g., BRIJ™ or MYRJ™ family PEG lipid). Pharmaceutical Compositions [0339] One aspect of the disclosure relates to pharmaceutical compositions comprising the recombinant RNA molecules described herein, or particles comprising a recombinant RNA molecule described herein, and methods for the treatment of cancer or vaccination. [0340] Compositions described herein can be formulated in any manner suitable for a desired delivery route. Typically, formulations include all physiologically acceptable compositions including derivatives or prodrugs, solvates, stereoisomers, racemates, or tautomers thereof with any pharmaceutically acceptable carriers, salts, diluents, and/or excipients. [0341] As used herein “pharmaceutically acceptable carrier, salts, diluent and/or excipient” includes without limitation any adjuvant, carrier, excipient, glidant, sweetening agent, diluent, preservative, dye/colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, surfactant, or emulsifier which has been approved by the United States Food and Drug Administration as being acceptable for use in humans or domestic animals. Exemplary pharmaceutically acceptable carriers include, but are not limited to, to sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; tragacanth; malt; gelatin; talc; cocoa butter, waxes, animal and vegetable fats, paraffins, silicones, bentonites, silicic acid, zinc oxide; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer’s solution; ethyl alcohol; phosphate buffer solutions; and any other compatible substances employed in pharmaceutical formulations. “Pharmaceutically acceptable salt” includes both acid and base addition salts. Pharmaceutically-acceptable salts include the acid addition salts (formed with the free amino groups of the protein) and which are formed with inorganic acids such as, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as, but not limited to, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4- acetamidobenzoic acid, camphoric acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, ptoluenesulfonic acid, trifluoroacetic acid, undecylenic acid, and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, deanol, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, benethamine, benzathine, ethylenediamine, glucosamine, methylglucamine, theobromine, triethanolamine, tromethamine, purines, piperazine, piperidine, N- ethylpiperidine, polyamine resins and the like. Particularly preferred organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. Other suitable carriers, salts, diluents, and/or excipients are well-known to those in the art. (See, e.g., Gennaro (ed.), Remington's Pharmaceutical Sciences (Mack Publishing Company, 19th ed. 1995).) Formulations can further include one or more excipients, preservatives, solubilizers, buffering agents, albumin to prevent protein loss on vial surfaces, etc. [0342] A pharmaceutical composition of the disclosure may be formulated in a dosage form selected from the group consisting of: an oral unit dosage form, an intravenous unit dosage form, an intranasal unit dosage form, a suppository unit dosage form, an intradermal unit dosage form, an intramuscular unit dosage form, an intraperitoneal unit dosage form, a subcutaneous unit dosage form, an epidural unit dosage form, a sublingual unit dosage form, and an intracerebral unit dosage form. The oral unit dosage form may be selected from the group consisting of: tablets, pills, pellets, capsules, powders, lozenges, granules, solutions, suspensions, emulsions, syrups, elixirs, sustained-release formulations, aerosols, and sprays. [0343] Pharmaceutical compositions can be supplied as a kit comprising a container that comprises the pharmaceutical composition as described herein. A pharmaceutical composition can be provided, for example, in the form of an injectable solution for single or multiple doses, or as a sterile powder that will be reconstituted before injection. Alternatively, such a kit can include a dry-powder disperser, liquid aerosol generator, or nebulizer for administration of a pharmaceutical composition. Such a kit can further comprise written information on indications and usage of the pharmaceutical composition. Methods of Use [0344] In some embodiments, the disclosure provides methods of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, of the disclosure. In some embodiments, the disease or disorder is a cancer. In some embodiments, the disease or disorder is an infectious disease. [0345] In some embodiments, the present disclosure provides methods of treating cancer in a subject in need thereof comprising administering an effective amount of the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, to the subject. [0346] In some embodiments, the present disclosure provides methods of vaccination in a subject in need thereof comprising administering an effective amount of the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, to the subject. [0347] The present disclosure provides methods of killing a cancerous cell or a target cell comprising exposing the cell to the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, under conditions sufficient for the intracellular delivery of the composition to the cancerous cell. As used herein, a “cancerous cell” or a “target cell” refers to a mammalian cell selected for treatment or administration with a polynucleotide or particle described herein, or composition thereof described herein. As used herein “killing a cancerous cell” refer specifically to the death of a cancerous cell by means of apoptosis or necrosis. Killing of a cancerous cell may be determined by methods known in the art including but not limited to, tumor size measurements, cell counts, and flow cytometry for the detection of cell death markers such as Annexin V and incorporation of propidium iodide. [0348] The present disclosure further provides methods of treating or preventing cancer in a subject in need thereof wherein an effective amount of the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, is administered to the subject. The route of administration will vary, naturally, with the location and nature of the disease being treated, and may include, for example intradermal, transdermal, subdermal, parenteral, nasal, intravenous, intramuscular, intranasal, subcutaneous, percutaneous, intratracheal, intraperitoneal, intratumoral, perfusion, lavage, direct injection, and oral administration. The encapsulated polynucleotide compositions described herein (e.g., virus particle or LNP) are particularly useful in the treatment of metastatic cancers, wherein systemic administration may be necessary to deliver the compositions to multiple organs and/or cell types. Therefore, in some embodiments, the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, described herein are administered systemically. [0349] An “effective amount” or an “effective dose,” used interchangeably herein, refers to an amount and or dose of the compositions described herein that results in an improvement, remediation, or prevention of the symptoms of the disease or condition. The improvement is any improvement or remediation of the disease or condition, or symptom of the disease or condition. The improvement is an observable or measurable improvement or may be an improvement in the general feeling of well-being of the subject. Thus, one of skill in the art realizes that a treatment may improve the disease condition but may not be a complete cure for the disease. Improvements in subjects may include, but are not limited to, decreased tumor burden, decreased tumor cell proliferation, increased tumor cell death, activation of immune pathways, increased time to tumor progression, decreased cancer pain, increased survival, or improvements in the quality of life. [0350] In some embodiments, administration of an effective dose may be achieved with administration a single dose of a composition described herein. As used herein, “dose” refers to the amount of a composition delivered at one time. In some embodiments, the dose of the recombinant RNA molecules is measured as the 50% Tissue culture Infective Dose (TCID₅₀). In some embodiments, the TCID₅₀ is at least about 10³-10⁹ TCID₅₀/mL, for example, at least about 10³ TCID₅₀/mL, about 10⁴ TCID₅₀/mL, about 10⁵ TCID₅₀/mL, about 10⁶ TCID₅₀/mL, about 10⁷ TCID₅₀/mL, about 10⁸ TCID₅₀/mL, or about 10⁹ TCID₅₀/mL. In some embodiments, a dose may be measured by the number of particles in a given volume (e.g., particles/mL). In some embodiments, a dose may be further refined by the genome copy number of the RNA polynucleotides described herein present in each particle (e.g., # of particles/mL, wherein each particle comprises at least one genome copy of the polynucleotide). In some embodiments, delivery of an effective dose may require administration of multiple doses of a composition described herein. As such, administration of an effective dose may require the administration of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, or more doses of a composition described herein. [0351] In embodiments wherein multiple doses of a composition described herein are administered, each dose need not be administered by the same actor and/or in the same geographical location. Further, the dosing may be administered according to a predetermined schedule. For example, the predetermined dosing schedule may comprise administering a dose of a composition described herein daily, every other day, weekly, bi-weekly, monthly, bi- monthly, annually, semi-annually, or the like. The predetermined dosing schedule may be adjusted as necessary for a given patient (e.g., the amount of the composition administered may be increased or decreased and/or the frequency of doses may be increased or decreased, and/or the total number of doses to be administered may be increased or decreased). [0352] As used herein “prevention” or “prophylaxis” can mean complete prevention of the symptoms of a disease, a delay in onset of the symptoms of a disease, or a lessening in the severity of subsequently developed disease symptoms. [0353] The term “subject” or “patient” as used herein, is taken to mean any mammalian subject to which a composition described herein is administered according to the methods described herein. In some embodiments, the methods of the present disclosure are employed to treat a human subject. The methods of the present disclosure may also be employed to treat non-human primates (e.g., monkeys, baboons, and chimpanzees), mice, rats, bovines, horses, cats, dogs, pigs, rabbits, goats, deer, sheep, ferrets, gerbils, guinea pigs, hamsters, bats, birds (e.g., chickens, turkeys, and ducks), fish, and reptiles. [0354] In some embodiments, treatment decisions for a particular cancer are made based on PVR expression, wherein the expression of PVR is determined in the cancer and the cancer is identified as sensitive or resistant to the therapeutic agent based on the level of PVR expression. In general, higher (% of positive cancer cells or intensity or both) expression of PVR indicates greater sensitivity to the therapeutic agent (the recombinant RNA molecule or the corresponding particle). [0355] In some embodiments, the present disclosure provides a method of treating a cancer in a subject in need thereof, comprising: (a) determining the expression level of PVR and/or the percentage of PVR positive cancer cells in the cancer; (b) classifying the cancer as sensitive to the therapeutic agent based on the expression level of PVR and/or the percentage of PVR positive cancer cells determined in (a); and (c) administering a therapeutically effective amount of the therapeutic agent to the subject if the cancer is classified as sensitive to the therapeutic agent infection in step (b). [0356] In some embodiments, the present disclosure provides a method of selecting a subject suffering from a cancer for treatment with the therapeutic agent (the recombinant RNA molecule or the corresponding particle), comprising: (a) determining the expression level of PVR and/or the percentage of PVR positive cancer cells in the cancer; (b) classifying the cancer as sensitive to the therapeutic agent based on the expression level of PVR and/or the percentage of PVR positive cancer cells as determined in (a); (c) selecting the subject for treatment with the therapeutic agent if the cancer is classified as sensitive to the therapeutic agent in (b); and (d) administering the therapeutic agent to the selected subject. [0357] The method may be a method of treating a subject having or at risk of having a disease or disorder that benefits from the therapeutic agent. Alternatively, the method may be a method of diagnosing a subject, in which case the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, may be a diagnostic agent. Combination Therapy [0358] In some embodiments, the disclosure provides methods of treating a cancer in a subject comprising administering to a subject suffering from the cancer (i) an effective amount of the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, and (ii) an effective amount of an immune checkpoint inhibitor. In some embodiments, the immune checkpoint inhibitor is an antibody or an antigen binding fragment thereof. In some embodiments, the immune checkpoint inhibitor binds to PD-1 (e.g., the inhibitor is an anti-PD-1 antibody). Anti-PD-1 antibodies are known in the art, for example, Nivolumab, Pembrolizumab, Lambrolizumab, Pidilzumab, Cemiplimab, and AMP-224 (AstraZeneca/MedImmune and GlaxoSmithKline), JTX-4014 by Jounce Therapeutics, Spartalizumab (PDR001, Novartis), Camrelizumab (SHR1210, Jiangsu HengRui Medicine Co., Ltd), Sintilimab (IBI308, Innovent and Eli Lilly), Tislelizumab (BGB-A317), Toripalimab (JS 001), Dostarlimab (TSR-042, WBP-285, GlaxoSmithKline), INCMGA00012 (MGA012, Incyte and MacroGenics), and AMP-514 (MEDI0680, AstraZeneca). In some embodiments, the immune checkpoint inhibitor binds to PD-L1 (e.g., the inhibitor is an anti-PD-L1 antibody). Anti-PD-L1 antibodies are known in the art, for example, MEDI-4736, MPDL3280A, Atezolizumab (Tecentriq, Roche Genentech), Avelumab (Bavencio, Merck Serono and Pfizer), and Durvalumab (Imfinzi, AstraZeneca). In some embodiments, the immune checkpoint inhibitor binds to CTLA4 (e.g., the inhibitor is an anti-CTLA4 antibody). Anti-CTLA4 antibodies are known in the art, for example, ipilumumab, tremelimumab, or any of the antibodies disclosed in WO2014/207063. In some embodiments, the immune checkpoint inhibitor is an anti-TIGIT antibody or fragment thereof. Anti-TIGIT antibodies are known in the art, for example tiragolumab (Roche), EOS-448 (iTeos Therapeutics), Vibostolimab (Merck), Domvanalimab (Arcus, Gilead), BMS-986207 (BMS), Etigilimab (Mereo), COM902 (Compugen), ASP8374 (Astellas), SEA-TGT (Seattle Genetics) BGB-A1217 (BeiGene), IBI- 939 (Innovent), and M6223 (EMD Serono). [0359] In some embodiments, both of 1) the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, and 2) the immune checkpoint inhibitor are concurrently administered. In some embodiments, these two therapeutic components are administered sequentially. In some embodiments, one or both therapeutic components are administered multiple times. [0360] In some embodiments, the disclosure provides methods of treating a cancer in a subject comprising administering to a subject suffering from the cancer (i) an effective amount of the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, and (ii) an effective amount of an engineered immune cell comprising an “engineered antigen receptor.” Engineered antigen receptors refer to non- naturally occurring antigen-specific receptors such as a chimeric antigen receptor (CAR) or a recombinant T cell receptor (TCR). In some embodiments, the engineered antigen receptor is a CAR comprising an extracellular antigen binding domain fused via hinge and transmembrane domains to a cytoplasmic domain comprising a signaling domain. In some embodiments, the CAR extracellular domain binds to an antigen expressed by a target cell in an MHC- independent manner leading to activation and proliferation of the engineered immune cell. In some embodiments, the extracellular domain of a CAR recognizes a tag fused to an antibody or antigen-binding fragment thereof. In such embodiments, the antigen-specificity of the CAR is dependent on the antigen-specificity of the labeled antibody, such that a single CAR construct can be used to target multiple different antigens by substituting one antibody for another (See e.g., US Patent Nos.9,233,125 and 9,624,279; US Patent Application Publication Nos. 20150238631 and 20180104354). In some embodiments, the extracellular domain of a CAR may comprise an antigen binding fragment derived from an antibody. Antigen binding domains that are useful in the present disclosure include, for example, scFvs; antibodies; antigen binding regions of antibodies; variable regions of the heavy/light chains; and single chain antibodies. [0361] In some embodiments, the intracellular signaling domain of a CAR may be derived from the TCR complex zeta chain (such as CD3ξ signaling domains), FcγRIII, FcεRI, or the T-lymphocyte activation domain. In some embodiments, the intracellular signaling domain of a CAR further comprises a costimulatory domain, for example a 4-1BB, CD28, CD40, MyD88, or CD70 domain. In some embodiments, the intracellular signaling domain of a CAR comprises two costimulatory domains, for example any two of 4-1BB, CD28, CD40, MyD88, or CD70 domains. Exemplary CAR structures and intracellular signaling domains are known in the art (See e.g., WO 2009/091826; US 20130287748; WO 2015/142675; WO 2014/055657; and WO 2015/090229, incorporated herein by reference). [0362] CARs specific for a variety of tumor antigens are known in the art, for example CD171-specific CARs (Park et al., Mol Ther (2007) 15(4):825-833), EGFRvIII-specific CARs (Morgan et al., Hum Gene Ther (2012) 23(10):1043-1053), EGF-R-specific CARs (Kobold et al., J Natl Cancer Inst (2014) 107(1):364), carbonic anhydrase K-specific CARs (Lamers et al., Biochem Soc Trans (2016) 44(3):951-959), FR-α-specific CARs (Kershaw et al., Clin Cancer Res (2006) 12(20):6106-6015), HER2-specific CARs (Ahmed et al., J Clin Oncol (2015) 33(15)1688-1696;Nakazawa et al., Mol Ther (2011) 19(12):2133-2143; Ahmed et al., Mol Ther (2009) 17(10):1779-1787; Luo et al., Cell Res (2016) 26(7):850-853; Morgan et al., Mol Ther (2010) 18(4):843-851; Grada et al., Mol Ther Nucleic Acids (2013) 9(2):32), CEA- specific CARs (Katz et al., Clin Cancer Res (2015) 21(14):3149-3159), IL13Rα2-specific CARs (Brown et al., Clin Cancer Res (2015) 21(18):4062-4072), GD2-specific CARs (Louis et al., Blood (2011) 118(23):6050-6056; Caruana et al., Nat Med (2015) 21(5):524-529), ErbB2-specific CARs (Wilkie et al., J Clin Immunol (2012) 32(5):1059-1070), VEGF-R- specific CARs (Chinnasamy et al., Cancer Res (2016) 22(2):436-447), FAP-specific CARs (Wang et al., Cancer Immunol Res (2014) 2(2):154-166), MSLN-specific CARs (Moon et al, Clin Cancer Res (2011) 17(14):4719-30), NKG2D-specific CARs (VanSeggelen et al., Mol Ther (2015) 23(10):1600-1610), CD19-specific CARs (Axicabtagene ciloleucel (Yescarta^®) and Tisagenlecleucel (Kymriah^®). See also L¸ i et al., J Hematol and Oncol (2018) 11(22), reviewing clinical trials of tumor-specific CARs. [0363] In some embodiments, the engineered antigen receptor is an engineered TCR. Engineered TCRs comprise TCRα and/or TCRβ chains that have been isolated and cloned from T cell populations recognizing a particular target antigen. For example, TCRα and/or TCRβ genes (i.e., TRAC and TRBC) can be cloned from T cell populations isolated from individuals with particular malignancies or T cell populations that have been isolated from humanized mice immunized with specific tumor antigens or tumor cells. Engineered TCRs recognize antigen through the same mechanisms as their endogenous counterparts (e.g., by recognition of their cognate antigen presented in the context of major histocompatibility complex (MHC) proteins expressed on the surface of a target cell). This antigen engagement stimulates endogenous signal transduction pathways leading to activation and proliferation of the TCR-engineered cells. [0364] Engineered TCRs specific for tumor antigens are known in the art, for example WT1-specific TCRs (JTCR016, Juno Therapeutics; WT1-TCRc4, described in US Patent Application Publication No. 20160083449), MART-1 specific TCRs (including the DMF4T clone, described in Morgan et al., Science 314 (2006) 126-129); the DMF5T clone, described in Johnson et al., Blood 114 (2009) 535-546); and the ID3T clone, described in van den Berg et al., Mol. Ther. 23 (2015) 1541-1550), gp100-specific TCRs (Johnson et al., Blood 114 (2009) 535-546), CEA-specific TCRs (Parkhurst et al., Mol Ther. 19 (2011) 620-626), NY- ESO and LAGE-1 specific TCRs (1G4T clone, described in Robbins et al., J Clin Oncol 26 (2011) 917-924; Robbins et al., Clin Cancer Res 21 (2015) 1019-1027; and Rapoport et al., Nature Medicine 21 (2015) 914-921), and MAGE-A3-specific TCRs (Morgan et al., J Immunother 36 (2013) 133-151) and Linette et al., Blood 122 (2013) 227-242). (See also, Debets et al., Seminars in Immunology 23 (2016) 10-21). [0365] In some embodiments, the engineered antigen receptor is directed against a target antigen selected from a cluster of differentiation molecule, such as CD3, CD4, CD8, CD16, CD24, CD25, CD33, CD34, CD45, CD64, CD71, CD78, CD80 (also known as B7-1), CD86 (also known as B7-2), CD96, , CD116, CD117, CD123, CD133, and CD138, CD371 (also known as CLL1); a tumor-associated surface antigen, such as 5T4, BCMA (also known as CD269 and TNFRSF17, UniProt# Q02223), carcinoembryonic antigen (CEA), carbonic anhydrase 9 (CAIX or MN/CAIX), CD19, CD20, CD22, CD30, CD40, disialogangliosides such as GD2, ELF2M, ductal-epithelial mucin, ephrin B2, epithelial cell adhesion molecule (EpCAM), ErbB2 (HER2/neu), FCRL5 (UniProt# Q68SN8), FKBP11 (UniProt# Q9NYL4), glioma-associated antigen, glycosphingolipids, gp36, GPRC5D (UniProt# Q9NZD1), mut hsp70-2, intestinal carboxyl esterase, IGF-I receptor, ITGA8 (UniProt# P53708), KAMP3, LAGE-1a, MAGE, mesothelin, neutrophil elastase, NKG2D, Nkp30, NY-ESO-1, PAP, prostase, prostate-carcinoma tumor antigen-1 (PCTA-1), prostate specific antigen (PSA), PSMA, prostein, RAGE-1, ROR1, RU1 (SFMBT1), RU2 (DCDC2), SLAMF7 (UniProt# Q9NQ25), survivin, TAG-72, and telomerase; a major histocompatibility complex (MHC) molecule presenting a tumor-specific peptide epitope; tumor stromal antigens, such as the extra domain A (EDA) and extra domain B (EDB) of fibronectin; the A1 domain of tenascin-C (TnC A1) and fibroblast associated protein (FAP); cytokine receptors, such as epidermal growth factor receptor (EGFR), EGFR variant III (EGFRvIII), TFGβ-R or components thereof such as endoglin; a major histocompatibility complex (MHC) molecule; a virus-specific surface antigen such as an HIV-specific antigen (such as HIV gp120); an EBV-specific antigen, a CMV-specific antigen, a HPV-specific antigen, a Lassa virus-specific antigen, an Influenza virus-specific antigen as well as any derivate or variant of these surface antigens. Administration Route and Dosage [0366] The recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, can be administered to subjects by a variety of administration modes, including, for example, by intramuscular, subcutaneous, intravenous, intra-atrial, intra-articular, parenteral, intranasal, intrapulmonary, transdermal, intrapleural, intrathecal, intratumoral, and oral routes of administration. For prevention and treatment purposes, a composition can be administered to a subject in a single bolus delivery, via continuous delivery (e.g., continuous transdermal delivery) over an extended time period, or in a repeated administration protocol (e.g., on an hourly, daily, weekly, or monthly basis). [0367] Administration can occur by injection, irrigation, inhalation, consumption, electro-osmosis, hemodialysis, iontophoresis, and other methods known in the art. The route of administration will vary, naturally, with the location and nature of the disease being treated, and may include, for example auricular, buccal, conjunctival, cutaneous, dental, endocervical, endosinusial, endotracheal, enteral, epidural, interstitial, intra-articular, intra-arterial, intra- abdominal, intraauricular, intrabiliary, intrabronchial, intrabursal, intracavernous, intracerebral, intracisternal, intracorneal, intracronal, intracoronary, intracranial, intradermal, intradiscal, intraductal, intraduodenal, intraduodenal, intradural, intraepicardial, intraepidermal, intraesophageal, intragastric, intragingival, intrahepatic, intraileal, intralesional, intralingual, intraluminal, intralymphatic, intramammary, intramedulleray, intrameningeal, instramuscular, intranasal, intranodal, intraocular, intraomentum, intraovarian, intraperitoneal, intrapericardial, intrapleural, intraprostatic, intrapulmonary, intraruminal, intrasinal, intraspinal, intrasynovial, intratendinous, intratesticular, intratracheal, intrathecal, intrathoracic, intratubular, intratumoral, intratympanic, intrauterine, intraperitoneal, intravascular, intraventricular, intravesical, intravestibular, intravenous, intravitreal, larangeal, nasal, nasogastric, oral, ophthalmic, oropharyngeal, parenteral, percutaneous, periarticular, peridural, perineural, periodontal, respiratory, retrotubular, rectal, spinal, subarachnoid, subconjunctival, subcutaneous, subdermal, subgingival, sublingual, submucosal, subretinal, topical, transdermal, transendocardial, transmucosal, transplacental, trantracheal, transtympanic, ureteral, urethral, and/or vaginal perfusion, lavage, direct injection, and oral administration. [0368] In some embodiments, the pharmaceutical composition of the disclosure is formulated for systemic administration. In some embodiments, the systemic administration comprises intravenous administration, intra-arterial administration, intraperitoneal administration, intramuscular administration, intradermal administration, subcutaneous administration, intranasal administration, oral administration, or a combination thereof. In some embodiments, the pharmaceutical composition is formulated for intravenous administration. In some embodiments, the pharmaceutical composition is formulated for local administration. In some embodiments, the pharmaceutical composition is formulated for intratumoral administration. [0369] In some embodiments, the disclosure provides methods of administering the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, to a subject, wherein the administration is systemic. In some embodiments, the administration is intravenous, intra-arterial, intraperitoneal, intramuscular, intradermal, subcutaneous, intranasal, oral, or a combination thereof. [0370] In some embodiments, the disclosure provides methods of administering the recombinant RNA molecule or the corresponding particle (e.g., virus particle or LNP), or the composition thereof, to a subject, wherein the administration is local. In some embodiments, the administration is intratumoral. [0371] Effective doses of the compositions of the disclosure vary depending upon many different factors, including means of administration, target site, physiological state of the subject, whether the subject is human or an animal, other medications administered, whether treatment is prophylactic or therapeutic, as well as the specific activity of the composition itself and its ability to elicit the desired response in the individual. In some embodiments, the subject is a human. In some embodiments, the subject can be a nonhuman mammal. Typically, dosage regimens are adjusted to provide an optimum therapeutic response, i.e., to optimize safety and efficacy. [0372] Determination of effective dosages in this context is typically based on animal model studies followed up by human clinical trials and is guided by determining effective dosages and administration protocols that significantly reduce the occurrence or severity of the subject disorder in model subjects. Compositions of the disclosure may be suitably administered to the subject at one time or over a series of treatments and may be administered to the subject at any time from diagnosis onwards. Compositions of the disclosure may be administered as the sole treatment, as a monotherapy, or in conjunction with other drugs or therapies, as a combinatorial therapy, useful in treating the condition in question. [0373] In some embodiments, the therapeutically effective amount of a composition of the disclosure is between about 1 ng/kg body weight to about 100 mg/kg body weight. In some embodiments, the range of a composition of the disclosure administered is from about 1 ng/kg body weight to about 1 μg/kg body weight, about 1 ng/kg body weight to about 100 ng/kg body weight, about 1 ng/kg body weight to about 10 ng/kg body weight, about 10 ng/kg body weight to about 1 μg/kg body weight, about 10 ng/kg body weight to about 100 ng/kg body weight, about 100 ng/kg body weight to about 1 μg/kg body weight, about 100 ng/kg body weight to about 10 pg/kg body weight, about 1 μg/kg body weight to about 10 pg/kg body weight, about 1 μg/kg body weight to about 100 pg/kg body weight, about 10 pg/kg body weight to about 100 pg/kg body weight, about 10 pg/kg body weight to about 1 mg/kg body weight, about 100 μg/kg body weight to about 10 mg/kg body weight, about 1 mg/kg body weight to about 100 mg/kg body weight, or about 10 mg/kg body weight to about 100 mg/kg body weight. Dosages within this range can be achieved by single or multiple administrations, including, e.g., multiple administrations per day or daily, weekly, bi-weekly, or monthly administrations. Compositions of the disclosure may be administered, as appropriate or indicated, as a single dose by bolus or by continuous infusion, or as multiple doses by bolus or by continuous infusion. Multiple doses may be administered, for example, multiple times per day, once daily, every 2, 3, 4, 5, 6 or 7 days, weekly, every 2, 3, 4, 5 or 6 weeks or monthly. In some embodiments, a composition of the disclosure is administered weekly. In some embodiments, a composition of the disclosure is administered biweekly. In some embodiments, a composition of the disclosure is administered every three weeks. However, other dosage regimens may be useful. The progress of this therapy is easily monitored by conventional techniques. [0374] For administration to a human adult subject, the therapeutically effective amount may be administered in doses in the range of 0.0006 mg to 1000 mg per dose, including but not limited to 0.0006 mg per dose, 0.001 mg per dose, 0.003 mg per dose, 0.006 mg per dose, 0.01 mg per dose, 0.03 mg per dose, 0.06 mg per dose, 0.1 mg per dose, 0.3 mg per dose, 0.6 mg per dose, 1 mg per dose, 3 mg per dose, 6 mg per dose, 10 mg per dose, 30 mg per dose, 60 mg per dose, 100 mg per dose, 300 mg per dose, 600 mg per dose and 1000 mg per dose, and multiple, usually consecutive daily doses may be administered in a course of treatment. In some embodiments, a composition of the disclosure is administered at a dose level of about 0.001 mg/kg/dose to about 10 mg/kg/dose, about 0.001 mg/kg/dose to about 6 mg/kg/dose, about 0.001 mg/kg/dose to about 3 mg/kg/dose, about 0.001 mg/kg/dose to about 1 mg/kg/dose, about 0.001 mg/kg/dose to about 0.6 mg/kg/dose, about 0.001 mg/kg/dose to about 0.3 mg/kg/dose, about 0.001 mg/kg/dose to about 0.1 mg/kg/dose, about 0.001 mg/kg/dose to about 0.06 mg/kg/dose, about 0.001 mg/kg/dose to about 0.03 mg/kg/dose, about 0.001 mg/kg/dose to about 0.01 mg/kg/dose, about 0.001 mg/kg/dose to about 0.006 mg/kg/dose, about 0.001 mg/kg/dose to about 0.003 mg/kg/dose, about 0.003 mg/kg/dose to about 10 mg/kg/dose, about 0.003 mg/kg/dose to about 6 mg/kg/dose, about 0.003 mg/kg/dose to about 3 mg/kg/dose, about 0.003 mg/kg/dose to about 1 mg/kg/dose, about 0.003 mg/kg/dose to about 0.6 mg/kg/dose, about 0.003 mg/kg/dose to about 0.3 mg/kg/dose, about 0.003 mg/kg/dose to about 0.1 mg/kg/dose, about 0.003 mg/kg/dose to about 0.06 mg/kg/dose, about 0.003 mg/kg/dose to about 0.03 mg/kg/dose, about 0.003 mg/kg/dose to about 0.01 mg/kg/dose, about 0.003 mg/kg/dose to about 0.006 mg/kg/dose, about 0.006 mg/kg/dose to about 10 mg/kg/dose, about 0.006 mg/kg/dose to about 6 mg/kg/dose, about 0.006 mg/kg/dose to about 3 mg/kg/dose, about 0.006 mg/kg/dose to about 1 mg/kg/dose, about 0.006 mg/kg/dose to about 0.6 mg/kg/dose, about 0.006 mg/kg/dose to about 0.3 mg/kg/dose, about 0.006 mg/kg/dose to about 0.1 mg/kg/dose, about 0.006 mg/kg/dose to about 0.06 mg/kg/dose, about 0.006 mg/kg/dose to about 0.03 mg/kg/dose, about 0.006 mg/kg/dose to about 0.01 mg/kg/dose, about 0.01 mg/kg/dose to about 10 mg/kg/dose, about 0.01 mg/kg/dose to about 6 mg/kg/dose, about 0.01 mg/kg/dose to about 3 mg/kg/dose, about 0.01 mg/kg/dose to about 1 mg/kg/dose, about 0.01 mg/kg/dose to about 0.6 mg/kg/dose, about 0.01 mg/kg/dose to about 0.3 mg/kg/dose, about 0.01 mg/kg/dose to about 0.1 mg/kg/dose, about 0.01 mg/kg/dose to about 0.06 mg/kg/dose, about 0.01 mg/kg/dose to about 0.03 mg/kg/dose, about 0.03 mg/kg/dose to about 10 mg/kg/dose, about 0.03 mg/kg/dose to about 6 mg/kg/dose, about 0.03 mg/kg/dose to about 3 mg/kg/dose, about 0.03 mg/kg/dose to about 1 mg/kg/dose, about 0.03 mg/kg/dose to about 0.6 mg/kg/dose, about 0.03 mg/kg/dose to about 0.3 mg/kg/dose, about 0.03 mg/kg/dose to about 0.1 mg/kg/dose, about 0.03 mg/kg/dose to about 0.06 mg/kg/dose, about 0.06 mg/kg/dose to about 10 mg/kg/dose, about 0.06 mg/kg/dose to about 6 mg/kg/dose, about 0.06 mg/kg/dose to about 3 mg/kg/dose, about 0.06 mg/kg/dose to about 1 mg/kg/dose, about 0.06 mg/kg/dose to about 0.6 mg/kg/dose, about 0.06 mg/kg/dose to about 0.3 mg/kg/dose, about 0.06 mg/kg/dose to about 0.1 mg/kg/dose, about 0.1 mg/kg/dose to about 10 mg/kg/dose, about 0.1 mg/kg/dose to about 6 mg/kg/dose, about 0.1 mg/kg/dose to about 3 mg/kg/dose, about 0.1 mg/kg/dose to about 1 mg/kg/dose, about 0.1 mg/kg/dose to about 0.6 mg/kg/dose, about 0.1 mg/kg/dose to about 0.3 mg/kg/dose, about 0.3 mg/kg/dose to about 10 mg/kg/dose, about 0.3 mg/kg/dose to about 6 mg/kg/dose, about 0.3 mg/kg/dose to about 3 mg/kg/dose, about 0.3 mg/kg/dose to about 1 mg/kg/dose, about 0.3 mg/kg/dose to about 0.6 mg/kg/dose, about 0.6 mg/kg/dose to about 10 mg/kg/dose, about 0.6 mg/kg/dose to about 6 mg/kg/dose, about 0.6 mg/kg/dose to about 3 mg/kg/dose, about 0.6 mg/kg/dose to about 1 mg/kg/dose, about 1 mg/kg/dose to about 10 mg/kg/dose, about 1 mg/kg/dose to about 6 mg/kg/dose, about 1 mg/kg/dose to about 3 mg/kg/dose, about 3 mg/kg/dose to about 10 mg/kg/dose, about 3 mg/kg/dose to about 6 mg/kg/dose, or about 6 mg/kg/dose to about 10 mg/kg/dose. In some embodiments, a composition of the disclosure is administered at a dose level of about 0.001 mg/kg/dose, about 0.003 mg/kg/dose, about 0.006 mg/kg/dose, about 0.01 mg/kg/dose, about 0.03 mg/kg/dose, about 0.06 mg/kg/dose, about 0.1 mg/kg/dose, about 0.3 mg/kg/dose, about 0.6 mg/kg/dose, about 1 mg/kg/dose, about 3 mg/kg/dose, about 6 mg/kg/dose, or about 10 mg/kg/dose. Compositions of the disclosure can be administered at different times of the day. In one embodiment the optimal therapeutic dose can be administered in the evening. In another embodiment the optimal therapeutic dose can be administered in the morning. As expected, the dosage will be dependent on the condition, size, age, and condition of the subject. [0375] Dosage of the pharmaceutical composition can be varied by the attending clinician to maintain a desired concentration at a target site. Higher or lower concentrations can be selected based on the mode of delivery. Dosage should also be adjusted based on the release rate of the administered formulation. [0376] In some embodiments, the pharmaceutical composition of the disclosure is administered to a subject multiple times (e.g., multiple doses). In some embodiments, the pharmaceutical composition is administered two or more times, three or more times, four or more times, etc. In some embodiments, administration of the pharmaceutical composition may be repeated once, twice, 3, 4, 5, 6, 7, 8, 9, 10, or more times. The pharmaceutical composition may be administered chronically or acutely, depending on its intended purpose. [0377] In some embodiments, the interval between two consecutive doses of the pharmaceutical composition is less than 4, less than 3, less than 2, or less than 1 weeks. In some embodiments, the interval between two consecutive doses is less than 3 weeks. In some embodiments, the interval between two consecutive doses is less than 2 weeks. In some embodiments, the interval between two consecutive doses is less than 1 week. In some embodiments, the interval between two consecutive doses is less than 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 days. In some embodiments, the interval between two consecutive doses of the pharmaceutical composition is at least 4, at least 3, at least 2, or at least 1 weeks. In some embodiments, the interval between two consecutive doses of the pharmaceutical composition of the disclosure is at least 3 weeks. In some embodiments, the interval between two consecutive doses of the pharmaceutical composition of the disclosure is at least 2 weeks. In some embodiments, the interval between two consecutive doses of the pharmaceutical composition of the disclosure is at least 1 week. In some embodiments, the interval between two consecutive doses of the pharmaceutical composition of the disclosure is at least 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 days. In some embodiments, the subject is administered a dose of the pharmaceutical composition of the disclosure once daily, every 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 days. In some embodiments, the subject is administered a dose of the pharmaceutical composition of the disclosure once every 4, 5, 6, 7, 8, 9, 10, 11, or 12 weeks. In some embodiments, the subject is administered a dose of the pharmaceutical composition of the disclosure once every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months. [0378] In some embodiments, administration of the pharmaceutical composition of the disclosure to a subject bearing a tumor inhibits growth of the tumor. In some embodiments, administration of the pharmaceutical composition inhibits growth of the tumor for at least 1 week, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 6 months, at least 9 months, at least 12 months, at least 2 years, or longer. In some embodiments, inhibiting growth of the tumor means controlling the size of the tumor within 100% of the size of the tumor just before administration of the pharmaceutical composition for a specified time period. In some embodiments, inhibiting growth of the tumor means controlling the size of the tumor within 110%, within 120%, within 130%, within 140%, or within 150%, of the size of the tumor just before administration of the pharmaceutical composition. [0379] In some embodiments, administration of the pharmaceutical composition to a subject bearing a tumor leads to tumor shrinkage or elimination. In some embodiments, administration of the pharmaceutical composition leads to tumor shrinkage or elimination for at least 1 week, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 6 months, at least 9 months, at least 12 months, at least 2 years, or longer. In some embodiments, administration of the pharmaceutical composition leads to tumor shrinkage or elimination within 1 week, within 2 weeks, within 3 weeks, within 4 weeks, within 1 month, within 2 months, within 3 months, within 4 months, within 6 months, within 9 months, within 12 months, or within 2 years. In some embodiments, tumor shrinkage means reducing the size of the tumor by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%, compared to the size of the tumor just before administration of the pharmaceutical composition. In some embodiments, tumor shrinkage means reducing the size of the tumor at least 30% compared to the size of the tumor just before administration of the pharmaceutical composition. [0380] In some embodiments, the method inhibits growth of the tumor for at least 1 week, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 6 months, at least 9 months, at least 12 months, at least 2 years, or longer. In some embodiments, inhibiting growth of the tumor means controlling the size of the tumor within 100% of the size of the tumor just before administration of the pharmaceutical composition for a specified time period. In some embodiments, inhibiting growth of the tumor means controlling the size of the tumor within 110%, within 120%, within 130%, within 140%, or within 150%, of the size of the tumor just before administration of the pharmaceutical composition. [0381] In some embodiments, the method results in tumor shrinkage or elimination for at least 1 week, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 6 months, at least 9 months, at least 12 months, at least 2 years, or longer. In some embodiments, the method results in tumor shrinkage or elimination within 1 week, within 2 weeks, within 3 weeks, within 4 weeks, within 1 month, within 2 months, within 3 months, within 4 months, within 6 months, within 9 months, within 12 months, or within 2 years. In some embodiments, tumor shrinkage means reducing the size of the tumor by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%, compared to the size of the tumor just before administration of the pharmaceutical composition. In some embodiments, tumor shrinkage means reducing the size of the tumor at least 30% compared to the size of the tumor just before administration of the pharmaceutical composition. [0382] In some embodiments, the method inhibits tumor metastasis for at least 1 week, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 6 months, at least 9 months, at least 12 months, at least 2 years, or longer. In some embodiments, the method results in tumor metastasis within 1 week, within 2 weeks, within 3 weeks, within 4 weeks, within 1 month, within 2 months, within 3 months, within 4 months, within 6 months, within 9 months, within 12 months, or within 2 years. In some embodiments, inhibiting tumor metastasis means reducing the size of the tumor at metastasized site(s) by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%, compared to the size of the tumor at metastasized site(s) just before administration of the pharmaceutical composition. In some embodiments, tumor shrinkage means reducing the size of the tumor at metastasized site(s) at least 30% compared to that just before administration of the pharmaceutical composition. [0383] In some embodiments, inhibiting tumor metastasis means reducing the likelihood of tumor metastasis by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%, compared to the likelihood of tumor metastasis without administration of the pharmaceutical composition. In some embodiments, inhibiting tumor metastasis means reducing the likelihood of tumor metastasis by at least 30% compared to that without administration of the pharmaceutical composition. [0384] In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the subject has a cancer, and wherein the method inhibits or slows the growth and/or metastasis of the cancer. Cancer [0385] “Cancer” herein refers to or describes the physiological condition in mammals that is typically characterized by unregulated cell growth. Examples of cancer include but are not limited to carcinoma, lymphoma, blastoma, sarcoma (including liposarcoma, osteogenic sarcoma, angiosarcoma, endotheliosarcoma, leiomyosarcoma, chordoma, lymphangiosarcoma, lymphangioendotheliosarcoma, rhabdomyosarcoma, fibrosarcoma, myxosarcoma, and chondrosarcoma), neuroendocrine tumors, mesothelioma, synovioma, schwannoma, meningioma, adenocarcinoma, melanoma, and leukemia or lymphoid malignancies. More particular examples of such cancers include squamous cell cancer (e.g., epithelial squamous cell cancer), lung cancer including small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung and squamous carcinoma of the lung, small cell lung carcinoma, cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney or renal cancer, prostate cancer, vulvar cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, testicular cancer, esophageal cancer, tumors of the biliary tract, Ewing’s tumor, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms’ tumor, testicular tumor, lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia, lymphoma, multiple myeloma, Waldenstrom’s macroglobulinemia, myelodysplastic disease, heavy chain disease, neuroendocrine tumors, Schwannoma, and other carcinomas, as well as head and neck cancer. In some embodiments, the cancer is a neuroendocrine cancer. Furthermore, benign (i.e., noncancerous) hyperproliferative diseases, disorders and conditions, including benign prostatic hypertrophy (BPH), meningioma, schwannoma, neurofibromatosis, keloids, myoma and uterine fibroids and others may also be treated using the disclosure disclosed herein. In some embodiments, the cancer is selected from small cell lung cancer (SCLC), small cell bladder cancer, large cell neuroendocrine carcinoma (LCNEC), castration- resistant small cell neuroendocrine prostate cancer (CRPC-NE), carcinoid (e.g., pulmonary carcinoid), and glioblastoma multiforme-IDH mutant (GBM-IDH mutant). [0386] In some embodiments, the cancer is a metastatic cancer. In some embodiments, the cancer has metastasized. In some embodiments, the cancer is a non-metastatic cancer. [0387] In some embodiments, the cancer is selected from the group consisting of lung cancer, breast cancer, colon cancer, pancreatic cancer, bladder cancer, renal cell carcinoma, ovarian cancer, gastric cancer and liver cancer. In some embodiments, the cancer is renal cell carcinoma, lung cancer, or liver cancer. In some embodiments, the lung cancer is NSCLC (non-small cell lung cancer). In some embodiments, the liver cancer is HCC (hepatocellular carcinoma). In some embodiments, the liver cancer is metastatic. In some embodiments, the breast cancer is TNBC (triple-negative breast cancer). In some embodiments, the bladder cancer is urothelial carcinoma. In some embodiments, the cancer is selected from the group consisting of breast cancer, esophageal cancer, stomach cancer, lung cancer, kidney cancer and skin cancer, and wherein the cancer has metastasized into liver. In some embodiments, the cancer is a metastasized cancer in the liver, wherein the cancer is originated from the group consisting of breast cancer, esophageal cancer, stomach cancer, lung cancer, kidney cancer and skin cancer. In some embodiments, the cancer is a hematologic cancer. In some embodiments, the hematologic cancer is multiple myeloma (see, e.g., Bradley, et al., Oncolytic Virotherapy, 2014:3 47–55, the content of which is incorporated by reference in its entirety). In some embodiments, the hematologic cancer is a leukemia or a lymphoma. FURTHER NUMBER EMBODIMENTS [0388] Further numbered embodiments of the invention are provided as follows: [0389] Embodiment 1. A recombinant RNA molecule encoding a viral genome of a chimeric virus derived from a coxsackievirus viral genome, wherein: i) a P1 region of the coxsackievirus viral genome is replaced with a P1 region of a poliovirus viral genome; and/or ii) a 2C region of the coxsackievirus viral genome is replaced with a 2C region of the poliovirus viral genome. [0390] Embodiment 2. The recombinant RNA molecule of Embodiment 1, wherein the P1 region of the coxsackievirus viral genome is replaced with the P1 region of the poliovirus viral genome, and wherein the P1 region of the coxsackievirus viral genome corresponds to nucleotides 714-3350 of SEQ ID NO: 1. [0391] Embodiment 3. The recombinant RNA molecule of Embodiment 1 or 2, wherein the 2C region of the coxsackievirus viral genome is replaced with the 2C region of the poliovirus viral genome, and wherein the 2C region of the coxsackievirus viral genome corresponds to nucleotides 4089-5075 of SEQ ID NO: 1. [0392] Embodiment 4. The recombinant RNA molecule of any one of Embodiments 1- 3, wherein the chimeric virus has poliovirus receptor (PVR) tropism. [0393] Embodiment 5. The recombinant RNA molecule of any one of Embodiments 1- 4, wherein the chimeric virus is capable of infecting a cell expressing a poliovirus receptor. [0394] Embodiment 6. The recombinant RNA molecule of any one of Embodiments 1- 5, wherein the chimeric virus is incapable of infecting a cell with no expression of a poliovirus receptor. [0395] Embodiment 7. The recombinant RNA molecule of any one of Embodiments 1- 6, wherein the coxsackievirus is a CVA21 strain. [0396] Embodiment 8. The recombinant RNA molecule of Embodiment 7, wherein the CVA21 strain is selected from KY strain, EF strain, and Kuykendall strain. [0397] Embodiment 9. The recombinant RNA molecule of Embodiment 7, wherein the CVA21 strain is KY strain. [0398] Embodiment 10. The recombinant RNA molecule of any one of Embodiments 1-9, wherein the coxsackievirus viral genome (excluding the P1 region and the 2C region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 1 (excluding the P1 region and the 2C region). [0399] Embodiment 11. The recombinant RNA molecule of any one of Embodiments 1-10, wherein the poliovirus viral genome is derived from PV1-Sabin strain. [0400] Embodiment 12. The recombinant RNA molecule of any one of Embodiments 1-11, wherein the P1 region of the poliovirus viral genome corresponds to nucleotides 743- 3385 of SEQ ID NO: 2. [0401] Embodiment 13. The recombinant RNA molecule of any one of Embodiments 1-12, wherein the P1 region of the poliovirus viral genome consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 743-3385 of SEQ ID NO: 2. [0402] Embodiment 14. The recombinant RNA molecule of any one of Embodiments 1-13, wherein the 2C region of the poliovirus viral genome corresponds to nucleotides 4124- 5110 of SEQ ID NO: 2. [0403] Embodiment 15. The recombinant RNA molecule of any one of Embodiments 1-14, wherein the 2C region of the poliovirus viral genome consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 4124-5110 of SEQ ID NO: 2. [0404] Embodiment 16. The recombinant RNA molecule of any one of Embodiments 1-15, wherein a cis-acting replication element (CRE) in the 2C region of the poliovirus viral genome is mutated, wherein the CRE corresponds to nucleotides 4444-4504 of SEQ ID NO: 2. [0405] Embodiment 17. The recombinant RNA molecule of Embodiment 16, wherein the mutated poliovirus CRE comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 mutations compared to SEQ ID NO: 10. [0406] Embodiment 18. The recombinant RNA molecule of Embodiment 16 or 17, wherein the mutated poliovirus CRE comprises or consists of SEQ ID NO: 4 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 4. [0407] Embodiment 19. The recombinant RNA molecule of any one of Embodiments 1-18, wherein the coxsackievirus viral genome comprises a coxsackievirus CRE located between stem loop I and stem loop II of an internal ribosome entry site (IRES) region located in a 5’ untranslated region (5’ UTR) of the coxsackievirus viral genome. [0408] Embodiment 20. A recombinant RNA molecule encoding a viral genome of a picornavirus, wherein the viral genome comprises a coxsackievirus CRE located between stem loop I and stem loop II of an internal ribosome entry site (IRES) region located in a 5’ untranslated region (5’ UTR) of the viral genome. [0409] Embodiment 21. The recombinant RNA molecule of Embodiment 20, wherein the 5’ UTR comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-713 of SEQ ID NO: 1. [0410] Embodiment 22. The recombinant RNA molecule of any one of Embodiments 1-21, wherein the viral genome comprises a coxsackievirus CRE located between the position corresponding to nucleotides 119 and 120 of SEQ ID NO: 1. [0411] Embodiment 23. The recombinant RNA molecule of any one of Embodiments 19-22, wherein the coxsackievirus CRE comprises or consists of SEQ ID NO: 5 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 5. [0412] Embodiment 24. The recombinant RNA molecule of any one of Embodiments 19-22, wherein the coxsackievirus CRE comprises or consists of SEQ ID NO: 6 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 6. [0413] Embodiment 25. The recombinant RNA molecule of any one of Embodiments 19-24, wherein the coxsackievirus CRE functions as a template for the uridylylation of VPg (3B) protein. [0414] Embodiment 26. The recombinant RNA molecule of any one of Embodiments 19-25, wherein the coxsackievirus CRE is the only active CRE of the viral genome. [0415] Embodiment 27. The recombinant RNA molecule of any one of Embodiments 1-26, comprising one or more miRNA target sequences; optionally wherein the recombinant RNA molecule comprises two copies of each of the miRNA target sequences. [0416] Embodiment 28. The recombinant RNA molecule of Embodiment 27, wherein the one or more miRNAs are selected from miR-124, miR-1, miR-143, miR-128, miR-219, miR-219a, miR-122, miR-204, miR-217, miR-137, miR-142, and miR-126. [0417] Embodiment 29. The recombinant RNA molecule of Embodiment 27 or 28, wherein the one or more miRNAs comprise at least one, at least two, at least three, or all four miRNAs selected from miR-1, miR-122, miR-124, and miR-137. [0418] Embodiment 30. The recombinant RNA molecule of Embodiment 27 or 28, wherein the one or more miRNAs comprise miR-124 and/or miR-122. [0419] Embodiment 31. The recombinant RNA molecule of any one of Embodiments 27-30, wherein the one or more miRNA target sequences are located between stem loop I and stem loop II of an IRES region located in a 5’ UTR of the coxsackievirus viral genome. [0420] Embodiment 32. The recombinant RNA molecule of any one of Embodiments 27-31, comprising the one or more miRNA target sequences flanking the 5’ and/or 3’ sides of the coxsackievirus CRE. [0421] Embodiment 33. The recombinant RNA molecule of Embodiment 32, wherein the coxsackievirus CRE and the adjacent miRNA target sequence(s) on the 5’ and/or 3’ sides are separated by 1-20 base pairs. [0422] Embodiment 34. The recombinant RNA molecule of any one of Embodiments 27-33, wherein the one or more miRNA target sequences are located between stem loop VI of an IRES region located in a 5’ UTR of the coxsackievirus viral genome and the P1 region. [0423] Embodiment 35. The recombinant RNA molecule of any one of Embodiments 27-34, wherein the one or more miRNA target sequences are located between the region corresponding to nucleotides 617 and 713 of SEQ ID NO: 1. [0424] Embodiment 36. The recombinant RNA molecule of any one of Embodiments 27-34, wherein the one or more miRNA target sequences are located between the region corresponding to nucleotides 634 and 698 of SEQ ID NO: 1. [0425] Embodiment 37. The recombinant RNA molecule of any one of Embodiments 1-36, wherein the coxsackievirus viral genome comprises a deletion or truncation of the region corresponding to nucleotides 635 and 697, inclusive of the endpoints, of SEQ ID NO: 1. [0426] Embodiment 38. The recombinant RNA molecule of Embodiment 37, wherein the truncation comprises at least 10 bp, at least 20 bp, at least 30 bp, at least 40 bp, at least 50 bp, or at least 60 bp, of the region corresponding to nucleotides 635 and 697, inclusive of the endpoints, of SEQ ID NO: 1. [0427] Embodiment 39. The recombinant RNA molecule of any one of Embodiments 27-38, wherein the one or more miRNA target sequences comprise SEQ ID NO: 30, or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 30. [0428] Embodiment 40. The recombinant RNA molecule of any one of Embodiments 27-38, wherein the one or more miRNA target sequences comprise SEQ ID NO: 8, or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 8. [0429] Embodiment 41. The recombinant RNA molecule of any one of Embodiments 1-40, comprising a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 28. [0430] Embodiment 42. A recombinant RNA molecule encoding a viral genome of a chimeric virus derived from a poliovirus viral genome, wherein an internal ribosome entry site (IRES) region of the poliovirus viral genome is replaced with an IRES region of a rhinovirus viral genome. [0431] Embodiment 43. The recombinant RNA molecule of Embodiment 42, wherein the IRES region of the poliovirus viral genome corresponds to nucleotides 111-742 of SEQ ID NO: 2. [0432] Embodiment 44. The recombinant RNA molecule of Embodiment 42 or 43, wherein the poliovirus is PV1-Sabin strain. [0433] Embodiment 45. The recombinant RNA molecule of any one of Embodiments 42-44, wherein the poliovirus viral genome (excluding the IRES region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 2 (excluding the IRES region). [0434] Embodiment 46. The recombinant RNA molecule of any one of Embodiments 42-45, wherein the rhinovirus viral genome is derived from human rhinovirus A30 (HRVA30). [0435] Embodiment 47. The recombinant RNA molecule of any one of Embodiments 42-46, wherein the IRES region of the rhinovirus viral genome corresponds to nucleotides 111- 602 of SEQ ID NO: 3. [0436] Embodiment 48. The recombinant RNA molecule of any one of Embodiments 42-47, wherein the IRES region of the rhinovirus viral genome comprises or consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 111-602 of SEQ ID NO: 3 or to nucleotides 120-602 of SEQ ID NO: 3. [0437] Embodiment 49. The recombinant RNA molecule of any one of Embodiments 42-48, wherein, compared to the poliovirus, the chimeric virus is more resistant to mutational reversion that results in higher virulence. [0438] Embodiment 50. The recombinant RNA molecule of any one of Embodiments 42-49, wherein the chimeric virus has lower infectivity of neuronal cells than the poliovirus. [0439] Embodiment 51. The recombinant RNA molecule of any one of Embodiments 42-50, wherein a cis-acting replication element (CRE) in the poliovirus viral genome is mutated, wherein the CRE corresponds to nucleotides 4444-4504 of SEQ ID NO: 2. [0440] Embodiment 52. The recombinant RNA molecule of any one of Embodiments 42-51, wherein the mutated CRE comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 mutations compared to SEQ ID NO: 10. [0441] Embodiment 53. The recombinant RNA molecule of Embodiment 52, wherein the mutated CRE comprises or consists of SEQ ID NO: 4 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutation compared to SEQ ID NO: 4. [0442] Embodiment 54. The recombinant RNA molecule of any one of Embodiments 42-53, wherein the poliovirus viral genome comprises a poliovirus CRE located between stem loop I and stem loop II of the IRES region located in the 5’ UTR of the viral genome. [0443] Embodiment 55. A recombinant RNA molecule encoding a viral genome of a picornavirus, wherein the viral genome comprises a poliovirus CRE located between stem loop I and stem loop II of an internal ribosome entry site (IRES) region located in a 5’ untranslated region (5’ UTR) of the viral genome. [0444] Embodiment 56. The recombinant RNA molecule of Embodiment 55, wherein the IRES region comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 111-602 of SEQ ID NO: 3 or to nucleotides 120-602 of SEQ ID NO: 3. [0445] Embodiment 57. The recombinant RNA molecule of Embodiment 55 or 56, wherein the 5’ UTR comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-602 of SEQ ID NO: 16 or to nucleotides 120-602 of SEQ ID NO: 16. [0446] Embodiment 58. The recombinant RNA molecule of any one of Embodiments 42-57, wherein the viral genome comprises a poliovirus CRE located between the region corresponding to nucleotides 89 and 120 of SEQ ID NO: 16. [0447] Embodiment 59. The recombinant RNA molecule of any one of Embodiments 42-57, wherein the viral genome comprises a poliovirus CRE located between the region corresponding to nucleotides 116 and 120 of SEQ ID NO: 16. [0448] Embodiment 60. The recombinant RNA molecule of any one of Embodiments 42-57, wherein the viral genome comprises a poliovirus CRE replacing the sequence corresponding to nucleotides 117 and 119 of SEQ ID NO: 16. [0449] Embodiment 61. The recombinant RNA molecule of any one of Embodiments 42-57, wherein the viral genome comprises a poliovirus CRE located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. [0450] Embodiment 62. The recombinant RNA molecule of any one of Embodiments 54-61, wherein the poliovirus CRE comprises or consists of SEQ ID NO: 7 or 25, or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 7 or 25. [0451] Embodiment 63. The recombinant RNA molecule of any one of Embodiments 54-62, wherein the poliovirus CRE functions as a template for the uridylylation of VPg (3B) protein. [0452] Embodiment 64. The recombinant RNA molecule of any one of Embodiments 54-63, wherein the poliovirus CRE is the only active CRE of the viral genome. [0453] Embodiment 65. The recombinant RNA molecule of any one of Embodiments 42-64, comprising one or more miRNA target sequences; optionally wherein the recombinant RNA molecule comprises two copies of each of the miRNA target sequences. [0454] Embodiment 66. The recombinant RNA molecule of Embodiment 65, wherein the one or more miRNAs are selected from miR-124, miR-1, miR-143, miR-128, miR-219, miR-219a, miR-122, miR-204, miR-217, miR-137, miR-142, and miR-126. [0455] Embodiment 67. The recombinant RNA molecule of Embodiment 65 or 66, wherein the one or more miRNAs comprise at least one, at least two, at least three, or all four miRNAs selected from miR-1, miR-122, miR-124, and miR-137. [0456] Embodiment 68. The recombinant RNA molecule of Embodiment 65 or 66, wherein the one or more miRNAs comprise miR-124 and/or miR-122. [0457] Embodiment 69. The recombinant RNA molecule of any one of Embodiments 65-68, wherein the one or more miRNA target sequences are located between stem loop I and stem loop II of the IRES region. [0458] Embodiment 70. The recombinant RNA molecule of any one of Embodiments 65-68, wherein the one or more miRNA target sequences are located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. [0459] Embodiment 71. The recombinant RNA molecule of any one of Embodiments 65-70, wherein the poliovirus viral genome comprises the one or more miRNA target sequences flanking 5’ and/or 3’ sides of the poliovirus CRE. [0460] Embodiment 72. The recombinant RNA molecule of Embodiment 71, wherein the poliovirus CRE and the adjacent miRNA target sequence(s) on the 5’ and/or 3’ sides are separated by 1-20 base pairs. [0461] Embodiment 73. The recombinant RNA molecule of any one of Embodiments 42-72, wherein the poliovirus viral genome comprises SEQ ID NO: 9 located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16. [0462] Embodiment 74. The recombinant RNA molecule of any one of Embodiments 42-73, comprising a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 26. [0463] Embodiment 75. The recombinant RNA molecule of any one of Embodiments 1-74, wherein the chimeric virus is oncolytic. [0464] Embodiment 76. The recombinant RNA molecule of any one of Embodiments 25-40 and 64-74, wherein replication of the chimeric virus is reduced or attenuated in a first cell compared to replication of the chimeric virus in a second cell, wherein the expression level of the one or more miRNAs in the first cell is higher than the expression level of the one or more miRNA in the second cell. [0465] Embodiment 77. The recombinant RNA molecule of Embodiment 76, wherein the expression level of the one or more miRNAs in the first cell is at least 50% higher, at least 100% higher, at least 2-fold higher, or at least 5-fold higher, than that in the second cell. [0466] Embodiment 78. The recombinant RNA molecule of Embodiment 76 or 77, wherein the first cell is a non-cancerous cell and the second cell is a cancerous cell. [0467] Embodiment 79. The recombinant RNA molecule of any one of Embodiments 1-78, wherein the recombinant RNA molecule comprises one or more payload-molecule encoding transgene(s). [0468] Embodiment 80. The recombinant RNA molecule of Embodiment 79, wherein the payload molecule(s) comprise a tumor antigen. [0469] Embodiment 81. The recombinant RNA molecule of Embodiment 79, wherein the payload molecule(s) comprise a MAGE family protein, survivin, p53 mutant, Kras mutant, or a neoantigen. [0470] Embodiment 82. The recombinant RNA molecule of any one of Embodiments 79-81, wherein the payload molecule(s) comprise an immune modulatory polypeptide. [0471] Embodiment 83. The recombinant RNA molecule of any one of Embodiments 1-82, comprising a 3’ polyA tail. [0472] Embodiment 84. The recombinant RNA molecule of Embodiment 83, wherein the polyA tail consists of about 70 adenine nucleotides in length. [0473] Embodiment 85. The recombinant RNA molecule of any one of Embodiments 1-84, wherein the recombinant RNA molecule comprises a nucleic acid analogue. [0474] Embodiment 86. A particle comprising the recombinant RNA molecule of any one of Embodiments 1-85. [0475] Embodiment 87. The particle of Embodiment 86, wherein the particle is a virus particle. [0476] Embodiment 88. The particle of Embodiment 87, wherein the virus particle has a tropism for poliovirus receptor (PVR). [0477] Embodiment 89. The particle of Embodiment 87 or 88, wherein the virus particle is produced by the recombinant RNA molecule and transcribed protein products thereof. [0478] Embodiment 90. The particle of Embodiment 86, wherein the particle is selected from the group consisting of a nanoparticle, an exosome, a liposome, and a lipoplex. [0479] Embodiment 91. The particle of Embodiment 86, wherein the particle is a lipid nanoparticle. [0480] Embodiment 92. The particle of any one of Embodiments 86-91, wherein the particle comprises a second nucleic acid molecule. [0481] Embodiment 93. The particle of any one of Embodiments 86-92, wherein contacting a eukaryotic cell with the particle results in production of infectious virus particles of the chimeric virus by the cell. [0482] Embodiment 94. The particle of Embodiment 93, wherein the eukaryotic cell expresses a poliovirus receptor. [0483] Embodiment 95. A pharmaceutical composition comprising the recombinant RNA molecule of any one of Embodiments 1-85 or the particle of any one of Embodiments 86-94, and a pharmaceutically acceptable carrier. [0484] Embodiment 96. A method of treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of the recombinant RNA molecule of any one of Embodiments 1-85, the particle of any one of Embodiments 86-94, or the pharmaceutical composition of Embodiment 95. [0485] Embodiment 97. A method of killing a cancer cell, comprising exposing the cancer cell to the recombinant RNA molecule of any one of Embodiments 1-85, the particle of any one of Embodiments 86-94, or the pharmaceutical composition of Embodiment 95. [0486] Embodiment 98. The method of Embodiment 96 or 97, wherein the cancer is colorectal cancer, gastric cancer, pancreatic cancer, or prostate cancer. [0487] Embodiment 99. The method of any one of Embodiments 96-98, wherein the cancer cell expresses a poliovirus receptor. [0488] Embodiment 100. The method of any one of Embodiments 96-99, wherein the administration comprises systemic administration. [0489] Embodiment 101. The method of any one of Embodiments 96-100, wherein the administration comprises intratumoral administration. [0490] Embodiment 102. The method of any one of Embodiments 96-101, further comprising administering an immune checkpoint inhibitor; optionally, wherein the immune checkpoint inhibitor is administered systemically. [0491] Embodiment 103. The method of Embodiment 102, wherein the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA4 inhibitor, a LAG-3 inhibitor, and/or a TIM-3 inhibitor. [0492] Embodiment 104. The method of any one of Embodiments 96-103, further comprising the step of testing the cancer cell to ascertain that it expresses PVR. [0493] Embodiment 105. A method of immunizing a subject against a disease, comprising administering to the subject an effective amount of the recombinant RNA molecule of any one of Embodiments 1-85, the particle of any one of Embodiments 86-94, or the pharmaceutical composition of Embodiment 95. [0494] Embodiment 106. The method of Embodiment 105, wherein the disease is a pathogenic infection, a bacterial infection, a parasitic infection or a viral infection. [0495] Embodiment 107. The method of Embodiment 105, wherein the disease is a viral infection; optionally wherein the disease is poliomyelitis. [0496] Embodiment 108. The method of Embodiment 105, wherein the disease is cancer. [0497] Embodiment 109. A recombinant DNA molecule encoding the recombinant RNA molecule of any one of Embodiments 1-85. [0498] Embodiment 110. The recombinant DNA molecule of Embodiment 109, comprising, from 5’ to 3’, a promoter, optionally a leader sequence, a ribozyme encoding sequence, the recombinant RNA molecule encoding sequence, a polyA tail, and a restriction enzyme recognition site. [0499] Embodiment 111. The recombinant DNA molecule of Embodiment 110, comprising the leader sequence, and wherein the leader sequence is less than 100 bp, less than 90bp, less than 80bp, less than 70 bp, less than 60 bp, less than 50 bp, or less than 40 bp in length. [0500] Embodiment 112. The recombinant DNA molecule of Embodiment 110 or 111, wherein the leader sequence comprises or consists of a polynucleotide sequence having at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity according to SEQ ID NO: 32 or 38. [0501] Embodiment 113. The recombinant DNA molecule of any one of Embodiments 110-112, wherein the leader sequence comprises or consists of SEQ ID NO: 32 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutation(s) thereto. [0502] Embodiment 114. The recombinant DNA molecule of any one of Embodiments 110-113, wherein the recombinant DNA molecule does not comprise additional nucleic acid between the promoter sequence and the leader sequence. [0503] Embodiment 115. The recombinant DNA molecule of any one of Embodiments 110-114, wherein the recombinant DNA molecule does not comprise additional nucleic acid between the leader sequence and the ribozyme encoding sequence. [0504] Embodiment 116. The recombinant DNA molecule of any one of Embodiments 110-115, wherein the ribozyme encoding sequence comprises or consists of a polynucleotide sequence (excluding P3 stem insert) having at least 80% identity to SEQ ID NO: 33 (excluding its P3 stem insert corresponding to nucleotides 49-54 of SEQ ID NO: 33). [0505] Embodiment 117. The recombinant DNA molecule of Embodiment 116, wherein the polynucleotide sequence (excluding P3 stem insert) is 100% identical, or has at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, or at most 11 mutations (insertions, deletions or substitutions), as compared to SEQ ID NO: 33 (excluding its P3 stem insert corresponding to nucleotides 49-54 of SEQ ID NO: 33). [0506] Embodiment 118. The recombinant DNA molecule of any one of Embodiments 110-117, wherein the ribozyme encoding sequence is 100% identical, or has at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, or at most 11 mutations (insertions, deletions or substitutions), as compared to any one of SEQ ID NO: 33-37. [0507] Embodiment 119. The recombinant DNA molecule of Embodiment 117 or 118, wherein the mutation(s) are substitution(s). [0508] Embodiment 120. The recombinant DNA molecule of any one of Embodiments 110-119, wherein the ribozyme encoding sequence comprises the polynucleotides “TTTATT” or “TTTGTT” at the positions corresponding to nucleotides 25-30 of SEQ ID NO: 33. [0509] Embodiment 121. The recombinant DNA molecule of Embodiment 120, wherein the ribozyme encoding sequence comprises the polynucleotides “TTTATT” at the positions corresponding to nucleotides 25-30 of SEQ ID NO: 33. [0510] Embodiment 122. The recombinant DNA molecule of any one of Embodiments 116-121, wherein the ribozyme encoding sequence comprises the P3 stem insert of about 1-30, about 1-20, about 6-20, or about 6-10 polynucleotides in length. [0511] Embodiment 123. The recombinant DNA molecule of any one of Embodiments 116-122, wherein the P3 stem insert is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 polynucleotides in length. [0512] Embodiment 124. The recombinant DNA molecule of any one of Embodiments 116-123, wherein the P3 stem insert is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 polynucleotides in length. [0513] Embodiment 125. The recombinant DNA molecule of any one of Embodiments 122-124, wherein the P3 stem insert comprises or consists of the polynucleotides

at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33. [0514] Embodiment 126. The recombinant DNA molecule of any one of Embodiments 122-124, wherein the P3 stem insert comprises or consists of the polynucleotides

(SEQ ID NO: 39) at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33. [0515] Embodiment 127. The recombinant DNA molecule of any one of Embodiments 122-124, wherein the P3 stem insert comprises or consists of the polynucleotides

(SEQ ID NO: 40) at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33. [0516] Embodiment 128. The recombinant DNA molecule of any one of Embodiments 110-127, wherein the recombinant DNA molecule does not comprise additional nucleic acid between the ribozyme encoding sequence and the polynucleotide sequence encoding the RNA molecule. [0517] Embodiment 129. The recombinant DNA molecule of any one of Embodiments 110-128, wherein cleavage at the ribozyme sequence and/or the restriction enzyme recognition site sequence produces native 5’ and/or 3’ ends of the synthetic RNA viral genome after transcription. [0518] Embodiment 130. The recombinant DNA molecule of any one of Embodiments 110-129, wherein the ribozyme encoding sequence comprises or consists of SEQ ID NO: 33 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutation(s) thereto. [0519] Embodiment 131. The recombinant DNA molecule of any one of Embodiments 110-130, wherein the polyA tail consists of about 70 adenine nucleotides in length. [0520] Embodiment 132. The recombinant DNA molecule of any one of Embodiments 110-131, wherein the restriction enzyme recognition site consists of a BsaI restriction site of SEQ ID NO: 22. [0521] Embodiment 133. The recombinant DNA molecule of any one of Embodiments 110-132, wherein the promoter comprises or consists of SEQ ID NO: 31 or a sequence having at most 3, at most 2, or at most 1 nucleotide mutation(s) thereto. [0522] Embodiment 134. The recombinant DNA molecule of any one of Embodiments 110-133, comprising no additional nucleotides in between the promoter, the optional leader sequence, the ribozyme encoding sequence, the recombinant RNA molecule encoding sequence, the polyA tail, and/or the restriction enzyme recognition site. [0523] Embodiment 135. The recombinant DNA molecule of any one of Embodiments 110-134, wherein the recombinant DNA molecule comprises a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 27 or 29. [0524] Embodiment 136. A method of producing the recombinant RNA molecule of any one of Embodiments 1-85, comprising transcription of a recombinant DNA molecule encoding the recombinant RNA molecule. [0525] Embodiment 137. A method of producing a recombinant RNA molecule, comprising transcription of the recombinant DNA molecule of any one of Embodiments 109- 135. [0526] Embodiment 138. The method of Embodiment 136 or 137, wherein the transcription comprises in vitro transcription using a T7 polymerase. [0527] Embodiment 139. A kit, comprising the recombinant RNA molecule of any one of Embodiments 1-85, the particle of any one of Embodiments 86-94, the pharmaceutical composition of Embodiment 95, or the recombinant DNA molecule of any one of Embodiments 109-135. EXAMPLES [0528] The following examples are given for the purpose of illustrating various embodiments of the disclosure and are not meant to limit the present disclosure in any fashion. The present examples along with the methods described herein are presently representative of preferred embodiments; are exemplary; and are not intended as limitations on the scope of the disclosure. Changes therein and other uses which are encompassed within the spirit of the disclosure as defined by the scope of the claims will occur to those skilled in the art. Example 1: Engineering of chimeric viruses KY-PVP12C and PV1-S/HRVA30-IRES [0529] Two chimeric viruses were engineered in this example, as shown in FIG.1. [0530] The first chimeric virus, KY-PVP12C (SEQ ID NO: 11), was derived from coxsackievirus CVA21-KY strain (SEQ ID NO: 1). The P1 (capsid) region of the CVA21-KY was replaced by the corresponding P1 region of poliovirus 1-Sabin strain (PV1-S; SEQ ID NO: 2) to create poliovirus receptor (PVR) tropism. The 2C region of CVA21-KY was also replaced by the 2C region from PV1-S, which improved viral fitness, viral assembly, and capsid packaging of viral genome. Compared to a control chimeric virus with only the P1 region replaced, the KY-PVP12C chimeric virus formed larger plagues and grew to ~50-fold higher titer. [0531] The second chimeric virus, PV1-S/HRVA30-IRES (SEQ ID NO: 16), was derived from PV1-Sabin (PV1-S; SEQ ID NO: 2). The IRES region of the PV1-S was replaced with that of human rhinovirus A30 (HRVA30) (SEQ ID NO: 3) to improve the safety profile. The PV1-S IRES region contains a point mutation that can be mutated to increase virus virulence. By replacing the IRES region with that of HRVA30, the chimeric virus has stable attenuation of the IRES and is resistant to mutational reversion. [0532] Viral fitness of the chimeric viruses was tested and compared to the parental viruses based on a viral plaque assay. As shown in FIG.2, parental and chimeric viruses were diluted for plaque titer analysis using NCI-H1299 cells (an NSCLC cell line) and, 72 hours post-infection, overlayed with 1% Methylcellulose and then stained with Crystal violet. In this assay, the presence of plaques confirmed virus viability and the sizes of the plaques provided a general indication of viral fitness. The results showed that, overall, both chimeric viruses had similar viability as the parental viruses, and the KY-PVP12C chimeric virus had a higher viral fitness compared to parental CVA21-KY virus according to its larger average plaque size. [0533] The IRES-mediated attenuation of PV1-S/HRVA30-IRES was tested in a cell survival assay. Three viruses were used: parental PV1-S, PV1-S/HRVA30-IRES, and another chimeric virus derived from PV1-S with HRV2-IRES (oncolytic poliovirus PVS-RIPO). 96- well plates were seeded with 150 ul media containing 10,000 cells per well. The next day, wells were infected with indicated virus at MOI dilutions starting with MOI 30 then serially diluted at 1:3 ratio.50ul of virus at each dilution was added to each well. One set was left uninfected and treated with media only. 72-hours post-infection, cell viability was determined by CellTiter-Glo® 2.0 cell viability assay and plotted as TCID50 curves. As shown in FIG. 3, HeLa cells (a representative cancer cell line) were sensitive to all three viruses. In comparison, for HEK-293 and SK-N-MC cells (both are neuronal-like cell lines), both chimeric viruses showed attenuation compared to the parental PV1-S. Notably, PV1-S/HRVA30-IRES chimeric virus was more potent towards HeLa cancer cell line as compared to the other chimeric virus comprising HRV2-IRES. [0534] The receptor tropism of KY-PVP12C were analyzed in a cell assay. HeLa cells or mouse B16 cells were plated at 10^5 cells/well in 12 well plates and infected at 10 MOI with the indicated virus for 72 hrs. before wells media was removed and stained with Crystal violet. The cleared wells indicated cell killing. As shown in FIG.4A, knocking out (KO) poliovirus receptor (PVR) in HeLa cells (“Hela PVR KO”) prevented KY-PVP12C infection, whereas the mouse B16 cell line expressing human PVR (B16-hPVR) allowed KY-PVP12C infection. On the other hand, parental CVA21-KY strain still infected HeLa cells with PVR knocked out. In FIG.4B, Western analysis of cell lysates confirmed the presence or absence of PVR in each cell line as expected. Thus, the results confirmed that the tropism of KY-PVP12C chimeric virus was switched to PVR. [0535] The ability to infect cancer cell lines was tested for both KY-PVP12C and PV1- S/HRVA30-IRES chimeric viruses. A total of 13 cell lines were used, including colorectal cancer cell lines Colo205, SW837, DLD-1, LS123, and SK-CO-1; gastric cancer cell lines NCI- N87 and HS 746T; pancreatic cancer cell lines BxPC-3, HPAF-II, and AsPC-1; and prostate cancer cell lines LNCaP clone FGC, 22rv1, and PC-3. PV1-S infection assay was performed at 0.1 MOI for 72 hours. Lysates of uninfected or PV1-S infected cells were probed for expression of PVR, Poliovirus proteins (EMD Millipore Ms x Poliovirus1 #MAB8560), and Actin (as a loading control). All these cell lines were confirmed to express human PVR (FIG. 5A and FIG.5B). And, except for BxPC-3, all other 12 cell lines were susceptible to PV1-S infection, as demonstrated by the presence of poliovirus protein after infection (FIG.5A and FIG.5B). [0536] For each of the 13 cancer cell lines, the TCID50s of PV1-S and both chimeric viruses were analyzed. Each cell line was infected with 1:3 serial dilutions of the indicated virus. Cell survival was determined by CellTiter-Glo® 2.0 cell viability assay 72 hours post- infection and compared to viability of uninfected cells. Cell survival rates were plotted as shown in FIGs. 6A-6D, and the TCID50s were summarized in FIG. 6E. Almost all these cancer cell lines were more sensitive to the two chimeric viruses, KY-PVP12C and PV1- S/HRVA30-IRES, than the parental viruses PV1-S or CVA21-KY. [0537] Overall, 12 out of 13 cancer cell lines were highly sensitive to KY-PVP12C chimeric virus, including three cancer cell lines that were resistant to PV1-S/HRVA30-IRES. And 10 out of 13 cancer cell lines were highly sensitive to PV1-S/HRVA30-IRES, which also showed higher potency than the parental viruses. Example 2: Optimization of Cis-acting Replication Element of the Chimeric Viruses [0538] Cis-acting replication element (CRE) of an RNA virus forms a secondary structure that facilitates viral replication. PV1-Sabin strain comprises an endogenous CRE (SEQ ID NO: 10) in the 2C region. At this position, this endogenous CRE may mediate undesirable recombination, resulting in the removal of the vital IRES region that mediate attenuation and cancer-specific translation of the virus. To prevent such recombination events that result in removal of the IRES, the endogenous CRE in the 2C region of PV1-S (SEQ ID NO: 10) could be mutated to SEQ ID NO: 4 in both chimeric viruses to destroy its native stem- loop structure and thereby eliminate its CRE function. Alternative CREs with stabilized stem- loop structure, “PV1-S CRE Stable” (SEQ ID NO: 7) and “CVA21-KY CRE Stable” (SEQ ID NO: 5), can be inserted into the viral genomes of PV1-S/HRVA30-IRES and KY-PVP12C, respectively. See FIGs.7A and 7C. Stop codons were also added to the stabilized CREs (see underlined base pairs in FIG. 7A) to further prevent relocation of the CRE. Vienna fold structure predictions (http://rna.tbi.univie.ac.at/cgi-bin/RNAWebSuite/RNAfold.cgi) and Gibbs free energy estimations for the CREs are shown in FIG. 7B. The stabilized CRE was inserted between the 5’ cloverleaf structure and viral IRES region, as shown in FIG.7C. [0539] In another design, a stabilized CRE (SEQ ID NO: 25) was inserted into the spacer I region of the PV1-S/HRVA30-IRES viral genome, replacing three endogenous base- pairs (at 117-119 of SEQ ID NO: 16) – see FIG.7E. This engineered virus, PV1-S/HRVA30- IRES CREmoved (SEQ ID NO: 26 with 70 bp polyA tail), was then tested for anti-cancer potency and plaque phenotype in a plaque assay using NCI-H1299 cells. As shown in FIG.7F, compared to the parental viral construct (PV1-S/HRVA30-IRES), the PV1-S/HRVA30-IRES CREmoved construct showed improved potency while maintaining viral fitness. Therefore, moving the CRE element to the 5’ spacer I region of the chimeric virus surprisingly improved viral potency against cancer cells. Example 3: miRNA Attenuation of the Chimeric Viruses [0540] miRNA target (miR-T) cassette(s) containing target sequences of tissue-specific miRNAs were inserted into the 5’ UTR of the chimeric viruses as an additional safety measure to protect normal tissues (e.g., neurons or liver cells) from viral infection. Such tissue-specific miRNAs include miR-124-3p and miR-122-5p. [0541] For KY-PVP12C chimeric virus: in the spacer 2 region after stem loop VI of the IRES, the nucleotides corresponding to base pairs 635-697 SEQ ID NO: 1 can be deleted and replaced with the sequence for the modified CRE and miR-T cassette for miR-122 and miR-124 (SEQ ID NO: 8). See FIG.8A. Additional KY-PVP12C viral constructs containing either the modified CRE or the miR-T cassettes were also generated as described below. [0542] For PV1-S/HRVA30-IRES chimeric virus: in the spacer 1 region after stem loop I (5’ cloverleaf), the modified CRE and miR-T cassette for miR-122 and miR-124 (SEQ ID NO: 9) were inserted in between the nucleotides corresponding to base pairs 118-119 of SEQ ID NO: 2. See FIG.8B. [0543] Schematics of the full chimeric virus constructs are shown in FIG.9A (for KY- PVP12C) and FIG.9B (for PV1-S/HRVA30-IRES), illustrating the mutated endogenous PV1- S CRE and the insertion locations of modified (stabilized) CRE and the miR-Ts cassettes in spacer 1 or spacer 2 region. The CRE modification or the miR-T cassette can be incorporated alone or in combination in either of the chimeric viruses. [0544] The following four different KY-PVP12C viral constructs were generated: KY-PVP12C: no CRE modification or miR-T insertion (SEQ ID NO: 11); KY-PVP12C CREmoved: with endogenous CRE removed from 2C and stabilized coxsackievirus CRE inserted at 5’ UTR (SEQ ID NO: 12); KY-PVP12C miR-T 122/124: inserted with miR-T cassette for miR-122 and miR-124 (SEQ ID NO: 13); KY-PVP12C CREmoved miR-T 122/124: with endogenous CRE removed from 2C, stabilized coxsackievirus CRE inserted at 5’ UTR, and insertion of miR-T cassette for miR- 122 and miR-124 (SEQ ID NO: 14); KY-PVP12C CREmoved miR-T 124/137: with endogenous CRE removed from 2C, stabilized coxsackievirus CRE inserted at 5’ UTR, and insertion of miR-T cassette for miR- 124 and miR-137 (SEQ ID NO: 15). [0545] Viral fitness was analyzed. For plaque titer assay, NCI-H1299 cells were infected by the indicated KY-PVP12C viruses and, 72 hrs. post-infection, overlayed with 1% Methylcellulose and then stained with Crystal violet, as shown in FIG. 10A. For TCID50 assay, HeLa cells were infected by the indicated viruses at serial 1:3 dilution, and cell survival at 72 hours post-infection was determined by CellTiter-Glo® 2.0 cell viability assay and compared to viability of uninfected cells, as shown by the plots in FIG. 10B. The results demonstrated that KY-PVP12C viruses with CRE and/or miR-T cassette modifications had similar viral fitness as the KY-PVP12C virus without these modifications. [0546] Next, miRNA attenuation was tested using either the KY-PVP12C CREmoved miR-T 122/124 virus or the KY-PVP12C CREmoved miR-T 124/137 virus in the miRNA mimic assay. NCI-H1299 cells were transfected with miRNA mimics corresponding to those for the miR-T cassettes or a negative control miRNA mimic four hours prior to infection with 1 MOI of virus.48 hours post-infection, cell survival was assayed by CellTiter-Glo® 2.0 cell viability assay and plotted as a percentage compared to uninfected non-transfected cells. As shown in FIG.11A and FIG.11B, the miR-T 122/124 cassette offered strong protection of cells in the presence of miR-124, and the miR-T 124/137 cassette offered strong protection of cells in the presence of either miR-124 or miR-137. Overall, these results demonstrated that the presence of specific miRNAs can efficiently protect cells/tissues from infection by a KY-PVP12C containing the corresponding target sequences of such miRNAs. [0547] To further improve the specificity of the KY-PVP12C virus towards cancer cells, a KY-PVP12C 4miR-T viral genome (SEQ ID NO: 28 with 70bp polyA tail) was constructed, which contains two copies of target sequences for 4 different miRNAs: miR-1, miR-122, miR-124, and miR-137, in the spacer 2 region of the IRES, replacing the nucleotides corresponding to positions 635-697 bp of SEQ ID NO: 11 (FIG.12A). The miR-T cassette has the RNA sequence of SEQ ID NO: 30. These miR target sequences should decrease the viral replication in normal tissues, such as heart (expressing miR-1), liver (expressing miR-122), and neuron (expressing miR-124 and miR-137), thereby improving the safety of the chimeric virus. [0548] In the NCI-H1299-based plaque assay, the KY-PVP12C 4miR-T virus displayed similar potency and plaque phenotype as the parental CVA21 KY virus and the previous KY- PVP12C miR-T 122/124 chimera virus (FIG. 12B). Therefore, expanding the miR target sequences in the spacer 2 region does not impact the viral fitness of the chimeric virus. [0549] Functionality of these miR target sequences was tested by mimic assay. Briefly, virus infected cells were transfected with mimics of miR-1, miR-122, miR-124, or miR-137 and then the viral cytotoxicity was evaluated. Each of the four miRNA mimics dramatically reduced viral cytotoxicity of KY-PVP12C 4miR-T virus (FIG.12C), demonstrating that each of the miRNA target sequences in the miR-T cassette is capable of control the replication of the viral genome. [0550] Similarly, the PV1-S/HRVA30-IRES (SEQ ID NO: 16) chimeric virus was engineered to mutate the endogenous CRE region and inserted with the CRE-miR-T-122/124 sequence (SEQ ID NO: 9) to create the PV1-S/HRVA30-IRES CREmoved miR-T 122/124 chimeric virus (SEQ ID NO: 17). Both viruses were subjected to the plaque titer assay (FIG. 13A) and HeLa TCID50 assay (FIG. 13B). And miRNA attenuation of the PV1-S/HRVA30- IRES CREmoved miR-T 122/124 chimeric virus was tested using both miR-122 and miR-124, as shown in FIG.14. The results demonstrated that the PV1-S/HRVA30-IRES CREmoved miR- T 122/124 chimeric virus retained the function of the parental PV1-S/HRVA30-IRES chimeric virus and gained miR-attenuation from the corresponding miRNAs. Example 4: In Vitro Transcription and Tumor-killing Efficacy of the KY-PVP12C 4miR- T Chimeric Virus [0551] The RNA viral genome of KY-PVP12C was generated by in vitro transcription (IVT) using a DNA template comprising, from 5’ to 3’, a T7 promoter (SEQ ID NO: 31), a leader sequence (SEQ ID NO: 32), an Env27 derived ribozyme encoding sequence (SEQ ID NO: 33), the viral genome encoding sequence (with 70 bp of polyA tail), and a 3’ BsaI restriction site (SEQ ID NO: 22). The DNA template sequence is SEQ ID NO: 29. [0552] To determine the cleavage efficiency at the 5’ end, test constructs that contain the T7 promoter, the leader sequence and ribozyme (Env27 derived or control), and ~250 bp of the 5’ end of the viral genome were prepared and their IVT products were analyzed using gel electrophoresis. As shown in FIG. 15, compared to a control template with an alternative 5’ ribozyme sequence derived from P. polymyxa pistol ribozyme, the Env27 derived ribozyme and corresponding leader sequence resulted in more efficient cleavage of the 5’ sequences, exposing the native 5’ end of the viral genome of either the KY-PVP12C chimeric virus or the parental CVA21 KY strain. [0553] Similarly, the same leader sequence and ribozyme derived from Env27 also improves cleavage efficiency during the IVT production of the PV1-S/HRVA30-IRES CREmoved RNA viral genome (data not shown). The IVT DNA template for PV1-S/HRVA30- IRES CREmoved is SEQ ID NO: 27. [0554] Large-scale cancer cell line TCID50 infection screen for KY-PVP12C 4miR-T virus was carried out by BIONESIS LLC (Bothell, WA). Briefly, 1,000 cells/10 µL/well were seeded in 384-well plate. The culture medium was OptiMEM with 2% FBS. Cells were incubated at 37 °C in 5% CO₂ overnight. Then, 2.5 µL of freshly prepared test article was serial diluted in OptiMEM media and added to the cells. The data points included 9-point dose- response plus zero in quadruplicate, 8-fold serial dilutions with a starting MOI = 30. The cells were then incubated at 37 °C in 5% CO₂ for 60 minutes, and 12.5 µL/well complete culture medium (2X, 20% FBS+1X P/S) was then added to the cells. The plates were then incubate at 37 °C in 5% CO₂ for 72 hours, at which point CellTiter Glow™ assay was performed. Cells were shook until lysed and analyzed at room temperature for data analysis. [0555] The TCID50 infection screen was performed in 22 breast, 15 colon/GI, 27 lung (5 SCLC; 22 NSCLC), 4 ovarian, 6 pancreatic, and 5 prostate cancer cell lines, including those in Table 6 below. The results (FIG.16A) demonstrate that KY-PVP12C 4miR-T is capable of killing various cancer cells, especially those from breast cancer, colon/GI cancer, lung cancer (e.g., NSCLC), and prostate cancer. Table 6. Cancer Cell Lines

[0556] The same cancer cell line TCID50 infection screen was also conducted for the PV1-S/HRVA30-IRES CREmoved virus. As shown in FIG. 16B, this virus is also capable of killing various cancer cells, especially those from breast cancer, colon/GI cancer, lung cancer (e.g., NSCLC), and prostate cancer. [0557] KY-PVP12C 4miR-T in vivo studies are being caried out in both xenograft and syngenetic animal models. Lipid nanoparticles (LNPs) comprising the RNA viral genome of KY-PVP12C 4miR-T are formulated for intravenous and/or intratumoral delivery. The LNP can be formulated with CAT7 cationic lipid (see Table 5 above). [0558] A B16 PVR cell line had been developed for the animal model using transgenic C57BL6 mice. The explanted tumor cells have about 95% PVR positivity (data not shown). The cell stock may be thawed in Blast media (20 ug/ml) for the first passage. The efficacy of LNP formulated with KY-PVP12C 4miR-T viral genome will be studied in this animal model. INCORPORATION BY REFERENCE [0559] All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entireties for all purposes. However, mention of any reference, article, publication, patent, patent publication, and patent application cited herein is not, and should not be taken as, an acknowledgment or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the world. [0560] While preferred embodiments of the present disclosure have been shown and described herein; it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed in practicing the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMS What is claimed is: 1. A recombinant RNA molecule encoding a viral genome of a chimeric virus derived from a coxsackievirus viral genome, wherein: i) a P1 region of the coxsackievirus viral genome is replaced with a P1 region of a poliovirus viral genome; and/or ii) a 2C region of the coxsackievirus viral genome is replaced with a 2C region of the poliovirus viral genome.

2. The recombinant RNA molecule of claim 1, wherein the P1 region of the coxsackievirus viral genome is replaced with the P1 region of the poliovirus viral genome, and wherein the P1 region of the coxsackievirus viral genome corresponds to nucleotides 714-3350 of SEQ ID NO: 1.

3. The recombinant RNA molecule of claim 1 or 2, wherein the 2C region of the coxsackievirus viral genome is replaced with the 2C region of the poliovirus viral genome, and wherein the 2C region of the coxsackievirus viral genome corresponds to nucleotides 4089-5075 of SEQ ID NO: 1.

4. The recombinant RNA molecule of any one of claims 1-3, wherein the chimeric virus has poliovirus receptor (PVR) tropism.

5. The recombinant RNA molecule of any one of claims 1-4, wherein the chimeric virus is capable of infecting a cell expressing a poliovirus receptor.

6. The recombinant RNA molecule of any one of claims 1-5, wherein the chimeric virus is incapable of infecting a cell with no expression of a poliovirus receptor.

7. The recombinant RNA molecule of any one of claims 1-6, wherein the coxsackievirus is a CVA21 strain.

8. The recombinant RNA molecule of claim 7, wherein the CVA21 strain is selected from KY strain, EF strain, and Kuykendall strain.

9. The recombinant RNA molecule of claim 7, wherein the CVA21 strain is KY strain.

10. The recombinant RNA molecule of any one of claims 1-9, wherein the coxsackievirus viral genome (excluding the P1 region and the 2C region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 1 (excluding the P1 region and the 2C region).

11. The recombinant RNA molecule of any one of claims 1-10, wherein the poliovirus viral genome is derived from PV1-Sabin strain.

12. The recombinant RNA molecule of any one of claims 1-11, wherein the P1 region of the poliovirus viral genome corresponds to nucleotides 743-3385 of SEQ ID NO: 2.

13. The recombinant RNA molecule of any one of claims 1-12, wherein the P1 region of the poliovirus viral genome consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 743-3385 of SEQ ID NO: 2.

14. The recombinant RNA molecule of any one of claims 1-13, wherein the 2C region of the poliovirus viral genome corresponds to nucleotides 4124-5110 of SEQ ID NO: 2.

15. The recombinant RNA molecule of any one of claims 1-14, wherein the 2C region of the poliovirus viral genome consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 4124-5110 of SEQ ID NO: 2.

16. The recombinant RNA molecule of any one of claims 1-15, wherein a cis-acting replication element (CRE) in the 2C region of the poliovirus viral genome is mutated, wherein the CRE corresponds to nucleotides 4444-4504 of SEQ ID NO: 2.

17. The recombinant RNA molecule of claim 16, wherein the mutated poliovirus CRE comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 mutations compared to SEQ ID NO: 10.

18. The recombinant RNA molecule of claim 16 or 17, wherein the mutated poliovirus CRE comprises or consists of SEQ ID NO: 4 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 4.

19. The recombinant RNA molecule of any one of claims 1-18, wherein the coxsackievirus viral genome comprises a coxsackievirus CRE located between stem loop I and stem loop II of an internal ribosome entry site (IRES) region located in a 5’ untranslated region (5’ UTR) of the coxsackievirus viral genome.

20. A recombinant RNA molecule encoding a viral genome of a picornavirus, wherein the viral genome comprises a coxsackievirus CRE located between stem loop I and stem loop II of an internal ribosome entry site (IRES) region located in a 5’ untranslated region (5’ UTR) of the viral genome.

21. The recombinant RNA molecule of claim 20, wherein the 5’ UTR comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-713 of SEQ ID NO: 1.

22. The recombinant RNA molecule of any one of claims 1-21, wherein the viral genome comprises a coxsackievirus CRE located between the position corresponding to nucleotides 119 and 120 of SEQ ID NO: 1.

23. The recombinant RNA molecule of any one of claims 19-22, wherein the coxsackievirus CRE comprises or consists of SEQ ID NO: 5 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 5.

24. The recombinant RNA molecule of any one of claims 19-22, wherein the coxsackievirus CRE comprises or consists of SEQ ID NO: 6 or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 6.

25. The recombinant RNA molecule of any one of claims 19-24, wherein the coxsackievirus CRE functions as a template for the uridylylation of VPg (3B) protein.

26. The recombinant RNA molecule of any one of claims 19-25, wherein the coxsackievirus CRE is the only active CRE of the viral genome.

27. The recombinant RNA molecule of any one of claims 1-26, comprising one or more miRNA target sequences; optionally wherein the recombinant RNA molecule comprises two copies of each of the miRNA target sequences.

28. The recombinant RNA molecule of claim 27, wherein the one or more miRNAs are selected from miR-124, miR-1, miR-143, miR-128, miR-219, miR-219a, miR-122, miR- 204, miR-217, miR-137, miR-142, and miR-126.

29. The recombinant RNA molecule of claim 27 or 28, wherein the one or more miRNAs comprise at least one, at least two, at least three, or all four miRNAs selected from miR-1, miR-122, miR-124, and miR-137.

30. The recombinant RNA molecule of claim 27 or 28, wherein the one or more miRNAs comprise miR-124 and/or miR-122.

31. The recombinant RNA molecule of any one of claims 27-30, wherein the one or more miRNA target sequences are located between stem loop I and stem loop II of an IRES region located in a 5’ UTR of the coxsackievirus viral genome.

32. The recombinant RNA molecule of any one of claims 27-31, comprising the one or more miRNA target sequences flanking the 5’ and/or 3’ sides of the coxsackievirus CRE.

33. The recombinant RNA molecule of claim 32, wherein the coxsackievirus CRE and the adjacent miRNA target sequence(s) on the 5’ and/or 3’ sides are separated by 1-20 base pairs.

34. The recombinant RNA molecule of any one of claims 27-33, wherein the one or more miRNA target sequences are located between stem loop VI of an IRES region located in a 5’ UTR of the coxsackievirus viral genome and the P1 region.

35. The recombinant RNA molecule of any one of claims 27-34, wherein the one or more miRNA target sequences are located between the region corresponding to nucleotides 617 and 713 of SEQ ID NO: 1.

36. The recombinant RNA molecule of any one of claims 27-34, wherein the one or more miRNA target sequences are located between the region corresponding to nucleotides 634 and 698 of SEQ ID NO: 1.

37. The recombinant RNA molecule of any one of claims 1-36, wherein the coxsackievirus viral genome comprises a deletion or truncation of the region corresponding to nucleotides 635 and 697, inclusive of the endpoints, of SEQ ID NO: 1.

38. The recombinant RNA molecule of claim 37, wherein the truncation comprises at least 10 bp, at least 20 bp, at least 30 bp, at least 40 bp, at least 50 bp, or at least 60 bp, of the region corresponding to nucleotides 635 and 697, inclusive of the endpoints, of SEQ ID NO: 1.

39. The recombinant RNA molecule of any one of claims 27-38, wherein the one or more miRNA target sequences comprise SEQ ID NO: 30, or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 30.

40. The recombinant RNA molecule of any one of claims 27-38, wherein the one or more miRNA target sequences comprise SEQ ID NO: 8, or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 8.

41. The recombinant RNA molecule of any one of claims 1-40, comprising a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 28.

42. A recombinant RNA molecule encoding a viral genome of a chimeric virus derived from a poliovirus viral genome, wherein an internal ribosome entry site (IRES) region of the poliovirus viral genome is replaced with an IRES region of a rhinovirus viral genome.

43. The recombinant RNA molecule of claim 42, wherein the IRES region of the poliovirus viral genome corresponds to nucleotides 111-742 of SEQ ID NO: 2.

44. The recombinant RNA molecule of claim 42 or 43, wherein the poliovirus is PV1-Sabin strain.

45. The recombinant RNA molecule of any one of claims 42-44, wherein the poliovirus viral genome (excluding the IRES region) comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 2 (excluding the IRES region).

46. The recombinant RNA molecule of any one of claims 42-45, wherein the rhinovirus viral genome is derived from human rhinovirus A30 (HRVA30).

47. The recombinant RNA molecule of any one of claims 42-46, wherein the IRES region of the rhinovirus viral genome corresponds to nucleotides 111-602 of SEQ ID NO: 3.

48. The recombinant RNA molecule of any one of claims 42-47, wherein the IRES region of the rhinovirus viral genome comprises or consists of a sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 111-602 of SEQ ID NO: 3 or to nucleotides 120-602 of SEQ ID NO: 3.

49. The recombinant RNA molecule of any one of claims 42-48, wherein, compared to the poliovirus, the chimeric virus is more resistant to mutational reversion that results in higher virulence.

50. The recombinant RNA molecule of any one of claims 42-49, wherein the chimeric virus has lower infectivity of neuronal cells than the poliovirus.

51. The recombinant RNA molecule of any one of claims 42-50, wherein a cis-acting replication element (CRE) in the poliovirus viral genome is mutated, wherein the CRE corresponds to nucleotides 4444-4504 of SEQ ID NO: 2.

52. The recombinant RNA molecule of any one of claims 42-51, wherein the mutated CRE comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 mutations compared to SEQ ID NO: 10.

53. The recombinant RNA molecule of claim 52, wherein the mutated CRE comprises or consists of SEQ ID NO: 4 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutation compared to SEQ ID NO: 4.

54. The recombinant RNA molecule of any one of claims 42-53, wherein the poliovirus viral genome comprises a poliovirus CRE located between stem loop I and stem loop II of the IRES region located in the 5’ UTR of the viral genome.

55. A recombinant RNA molecule encoding a viral genome of a picornavirus, wherein the viral genome comprises a poliovirus CRE located between stem loop I and stem loop II of an internal ribosome entry site (IRES) region located in a 5’ untranslated region (5’ UTR) of the viral genome.

56. The recombinant RNA molecule of claim 55, wherein the IRES region comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 111-602 of SEQ ID NO: 3 or to nucleotides 120-602 of SEQ ID NO: 3.

57. The recombinant RNA molecule of claim 55 or 56, wherein the 5’ UTR comprises a polynucleotide sequence having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to nucleotides 1-602 of SEQ ID NO: 16 or to nucleotides 120-602 of SEQ ID NO: 16.

58. The recombinant RNA molecule of any one of claims 42-57, wherein the viral genome comprises a poliovirus CRE located between the region corresponding to nucleotides 89 and 120 of SEQ ID NO: 16.

59. The recombinant RNA molecule of any one of claims 42-57, wherein the viral genome comprises a poliovirus CRE located between the region corresponding to nucleotides 116 and 120 of SEQ ID NO: 16.

60. The recombinant RNA molecule of any one of claims 42-57, wherein the viral genome comprises a poliovirus CRE replacing the sequence corresponding to nucleotides 117 and 119 of SEQ ID NO: 16.

61. The recombinant RNA molecule of any one of claims 42-57, wherein the viral genome comprises a poliovirus CRE located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16.

62. The recombinant RNA molecule of any one of claims 54-61, wherein the poliovirus CRE comprises or consists of SEQ ID NO: 7 or 25, or a sequence having at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutations compared to SEQ ID NO: 7 or 25.

63. The recombinant RNA molecule of any one of claims 54-62, wherein the poliovirus CRE functions as a template for the uridylylation of VPg (3B) protein.

64. The recombinant RNA molecule of any one of claims 54-63, wherein the poliovirus CRE is the only active CRE of the viral genome.

65. The recombinant RNA molecule of any one of claims 42-64, comprising one or more miRNA target sequences; optionally wherein the recombinant RNA molecule comprises two copies of each of the miRNA target sequences.

66. The recombinant RNA molecule of claim 65, wherein the one or more miRNAs are selected from miR-124, miR-1, miR-143, miR-128, miR-219, miR-219a, miR-122, miR- 204, miR-217, miR-137, miR-142, and miR-126.

67. The recombinant RNA molecule of claim 65 or 66, wherein the one or more miRNAs comprise at least one, at least two, at least three, or all four miRNAs selected from miR-1, miR-122, miR-124, and miR-137.

68. The recombinant RNA molecule of claim 65 or 66, wherein the one or more miRNAs comprise miR-124 and/or miR-122.

69. The recombinant RNA molecule of any one of claims 65-68, wherein the one or more miRNA target sequences are located between stem loop I and stem loop II of the IRES region.

70. The recombinant RNA molecule of any one of claims 65-68, wherein the one or more miRNA target sequences are located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16.

71. The recombinant RNA molecule of any one of claims 65-70, wherein the poliovirus viral genome comprises the one or more miRNA target sequences flanking 5’ and/or 3’ sides of the poliovirus CRE.

72. The recombinant RNA molecule of claim 71, wherein the poliovirus CRE and the adjacent miRNA target sequence(s) on the 5’ and/or 3’ sides are separated by 1-20 base pairs.

73. The recombinant RNA molecule of any one of claims 42-72, wherein the poliovirus viral genome comprises SEQ ID NO: 9 located between the region corresponding to nucleotides 118 and 119 of SEQ ID NO: 16.

74. The recombinant RNA molecule of any one of claims 42-73, comprising a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 26.

75. The recombinant RNA molecule of any one of claims 1-74, wherein the chimeric virus is oncolytic.

76. The recombinant RNA molecule of any one of claims 25-40 and 64-74, wherein replication of the chimeric virus is reduced or attenuated in a first cell compared to replication of the chimeric virus in a second cell, wherein the expression level of the one or more miRNAs in the first cell is higher than the expression level of the one or more miRNA in the second cell.

77. The recombinant RNA molecule of claim 76, wherein the expression level of the one or more miRNAs in the first cell is at least 50% higher, at least 100% higher, at least 2-fold higher, or at least 5-fold higher, than that in the second cell.

78. The recombinant RNA molecule of claim 76 or 77, wherein the first cell is a non- cancerous cell and the second cell is a cancerous cell.

79. The recombinant RNA molecule of any one of claims 1-78, wherein the recombinant RNA molecule comprises one or more payload-molecule encoding transgene(s).

80. The recombinant RNA molecule of claim 79, wherein the payload molecule(s) comprise a tumor antigen.

81. The recombinant RNA molecule of claim 79, wherein the payload molecule(s) comprise a MAGE family protein, survivin, p53 mutant, Kras mutant, or a neoantigen.

82. The recombinant RNA molecule of any one of claims 79-81, wherein the payload molecule(s) comprise an immune modulatory polypeptide.

83. The recombinant RNA molecule of any one of claims 1-82, comprising a 3’ polyA tail.

84. The recombinant RNA molecule of claim 83, wherein the polyA tail consists of about 70 adenine nucleotides in length.

85. The recombinant RNA molecule of any one of claims 1-84, wherein the recombinant RNA molecule comprises a nucleic acid analogue.

86. A particle comprising the recombinant RNA molecule of any one of claims 1-85.

87. The particle of claim 86, wherein the particle is a virus particle.

88. The particle of claim 87, wherein the virus particle has a tropism for poliovirus receptor (PVR).

89. The particle of claim 87 or 88, wherein the virus particle is produced by the recombinant RNA molecule and transcribed protein products thereof.

90. The particle of claim 86, wherein the particle is selected from the group consisting of a nanoparticle, an exosome, a liposome, and a lipoplex.

91. The particle of claim 86, wherein the particle is a lipid nanoparticle.

92. The particle of any one of claims 86-91, wherein the particle comprises a second nucleic acid molecule.

93. The particle of any one of claims 86-92, wherein contacting a eukaryotic cell with the particle results in production of infectious virus particles of the chimeric virus by the cell.

94. The particle of claim 93, wherein the eukaryotic cell expresses a poliovirus receptor.

95. A pharmaceutical composition comprising the recombinant RNA molecule of any one of claims 1-85 or the particle of any one of claims 86-94, and a pharmaceutically acceptable carrier.

96. A method of treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of the recombinant RNA molecule of any one of claims 1-85, the particle of any one of claims 86-94, or the pharmaceutical composition of claim 95.

97. A method of killing a cancer cell, comprising exposing the cancer cell to the recombinant RNA molecule of any one of claims 1-85, the particle of any one of claims 86-94, or the pharmaceutical composition of claim 95.

98. The method of claim 96 or 97, wherein the cancer is colorectal cancer, gastric cancer, pancreatic cancer, or prostate cancer.

99. The method of any one of claims 96-98, wherein the cancer cell expresses a poliovirus receptor.

100. The method of any one of claims 96-99, wherein the administration comprises systemic administration.

101. The method of any one of claims 96-100, wherein the administration comprises intratumoral administration.

102. The method of any one of claims 96-101, further comprising administering an immune checkpoint inhibitor; optionally, wherein the immune checkpoint inhibitor is administered systemically.

103. The method of claim 102, wherein the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA4 inhibitor, a LAG-3 inhibitor, and/or a TIM-3 inhibitor.

104. The method of any one of claims 96-103, further comprising the step of testing the cancer cell to ascertain that it expresses PVR.

105. A method of immunizing a subject against a disease, comprising administering to the subject an effective amount of the recombinant RNA molecule of any one of claims 1-85, the particle of any one of claims 86-94, or the pharmaceutical composition of claim 95.

106. The method of claim 105, wherein the disease is a pathogenic infection, a bacterial infection, a parasitic infection or a viral infection.

107. The method of claim 105, wherein the disease is a viral infection; optionally wherein the disease is poliomyelitis.

108. The method of claim 105, wherein the disease is cancer.

109. A recombinant DNA molecule encoding the recombinant RNA molecule of any one of claims 1-85.

110. The recombinant DNA molecule of claim 109, comprising, from 5’ to 3’, a promoter, optionally a leader sequence, a ribozyme encoding sequence, the recombinant RNA molecule encoding sequence, a polyA tail, and a restriction enzyme recognition site.

111. The recombinant DNA molecule of claim 110, comprising the leader sequence, and wherein the leader sequence is less than 100 bp, less than 90bp, less than 80bp, less than 70 bp, less than 60 bp, less than 50 bp, or less than 40 bp in length.

112. The recombinant DNA molecule of claim 110 or 111, wherein the leader sequence comprises or consists of a polynucleotide sequence having at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity according to SEQ ID NO: 32 or 38.

113. The recombinant DNA molecule of any one of claims 110-112, wherein the leader sequence comprises or consists of SEQ ID NO: 32 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutation(s) thereto.

114. The recombinant DNA molecule of any one of claims 110-113, wherein the recombinant DNA molecule does not comprise additional nucleic acid between the promoter sequence and the leader sequence.

115. The recombinant DNA molecule of any one of claims 110-114, wherein the recombinant DNA molecule does not comprise additional nucleic acid between the leader sequence and the ribozyme encoding sequence.

116. The recombinant DNA molecule of any one of claims 110-115, wherein the ribozyme encoding sequence comprises or consists of a polynucleotide sequence (excluding P3 stem insert) having at least 80% identity to SEQ ID NO: 33 (excluding its P3 stem insert corresponding to nucleotides 49-54 of SEQ ID NO: 33).

117. The recombinant DNA molecule of claim 116, wherein the polynucleotide sequence (excluding P3 stem insert) is 100% identical, or has at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, or at most 11 mutations (insertions, deletions or substitutions), as compared to SEQ ID NO: 33 (excluding its P3 stem insert corresponding to nucleotides 49-54 of SEQ ID NO: 33).

118. The recombinant DNA molecule of any one of claims 110-117, wherein the ribozyme encoding sequence is 100% identical, or has at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, or at most 11 mutations (insertions, deletions or substitutions), as compared to any one of SEQ ID NO: 33-37.

119. The recombinant DNA molecule of claim 117 or 118, wherein the mutation(s) are substitution(s).

120. The recombinant DNA molecule of any one of claims 110-119, wherein the ribozyme encoding sequence comprises the polynucleotides

or

at the positions corresponding to nucleotides 25-30 of SEQ ID NO: 33.

121. The recombinant DNA molecule of claim 120, wherein the ribozyme encoding sequence comprises the polynucleotides at the positions corresponding to

nucleotides 25-30 of SEQ ID NO: 33.

122. The recombinant DNA molecule of any one of claims 116-121, wherein the ribozyme encoding sequence comprises the P3 stem insert of about 1-30, about 1-20, about 6-20, or about 6-10 polynucleotides in length.

123. The recombinant DNA molecule of any one of claims 116-122, wherein the P3 stem insert is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 polynucleotides in length.

124. The recombinant DNA molecule of any one of claims 116-123, wherein the P3 stem insert is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 polynucleotides in length.

125. The recombinant DNA molecule of any one of claims 122-124, wherein the P3 stem insert comprises or consists of the polynucleotides

at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33.

126. The recombinant DNA molecule of any one of claims 122-124, wherein the P3 stem insert comprises or consists of the polynucleotides

(SEQ ID NO: 39) at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33.

127. The recombinant DNA molecule of any one of claims 122-124, wherein the P3 stem insert comprises or consists of the polynucleotides

(SEQ ID NO: 40) at the region corresponding to nucleotides 49-54 of SEQ ID NO: 33.

128. The recombinant DNA molecule of any one of claims 110-127, wherein the recombinant DNA molecule does not comprise additional nucleic acid between the ribozyme encoding sequence and the polynucleotide sequence encoding the RNA molecule.

129. The recombinant DNA molecule of any one of claims 110-128, wherein cleavage at the ribozyme sequence and/or the restriction enzyme recognition site sequence produces native 5’ and/or 3’ ends of the synthetic RNA viral genome after transcription.

130. The recombinant DNA molecule of any one of claims 110-129, wherein the ribozyme encoding sequence comprises or consists of SEQ ID NO: 33 or a sequence having at most 6, at most 5, at most 4, at most 3, at most 2, or at most 1 nucleotide mutation(s) thereto.

131. The recombinant DNA molecule of any one of claims 110-130, wherein the polyA tail consists of about 70 adenine nucleotides in length.

132. The recombinant DNA molecule of any one of claims 110-131, wherein the restriction enzyme recognition site consists of a BsaI restriction site of SEQ ID NO: 22.

133. The recombinant DNA molecule of any one of claims 110-132, wherein the promoter comprises or consists of SEQ ID NO: 31 or a sequence having at most 3, at most 2, or at most 1 nucleotide mutation(s) thereto.

134. The recombinant DNA molecule of any one of claims 110-133, comprising no additional nucleotides in between the promoter, the optional leader sequence, the ribozyme encoding sequence, the recombinant RNA molecule encoding sequence, the polyA tail, and/or the restriction enzyme recognition site.

135. The recombinant DNA molecule of any one of claims 110-134, wherein the recombinant DNA molecule comprises a sequence (excluding the optional region of payload-molecule encoding transgene(s)) having at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to SEQ ID NO: 27 or 29.

136. A method of producing the recombinant RNA molecule of any one of claims 1-85, comprising transcription of a recombinant DNA molecule encoding the recombinant RNA molecule.

137. A method of producing a recombinant RNA molecule, comprising transcription of the recombinant DNA molecule of any one of claims 109-135.

138. The method of claim 136 or 137, wherein the transcription comprises in vitro transcription using a T7 polymerase.

139. A kit, comprising the recombinant RNA molecule of any one of claims 1-85, the particle of any one of claims 86-94, the pharmaceutical composition of claim 95, or the recombinant DNA molecule of claim 109-135.