CIRCULAR RNA DERIVED FROM RNA VIRUSES AND RELATED COMPOSITIONS AND METHODS
Provided herein are methods and compositions for reducing the proviral effect of a virus-derived circular RNA on a target cell through the use of an agent that blocks a proviral function of the virus-derived circular RNA. Also, provided herein are methods of treating a cytoplasmic or nuclear RNA viral infection in a subject and compositions to block a proviral effect of a virus-derived circular RNA or compositions that promote an antiviral effect of the virus-derived circular RNA.
1 . A method of reducing a proviral effect of a virus-derived circular RNA on a target cell, the method comprising:
(a) identifying a virus-derived circular RNA having a proviral effect, wherein the virus-derived circular RNA is derived from a genome of an RNA virus; and
(b) contacting the target cell with an agent that blocks a proviral function of the virus-derived circular RNA.
2 . The method of claim 1 , wherein the RNA virus is a cytoplasmic RNA virus selected from the group consisting of a flavivirus, a coronavirus, an enterovirus, a reovirus, a picornavirus, and a togavirus.
3 . The method of claim 2 , wherein the cytoplasmic RNA virus is a flavivirus and wherein the flavivirus is selected from the group consisting of hepatitis C virus, Zika virus, West Nile virus, Dengue virus, yellow fever virus, and St. Louis encephalitis virus.
4 . (canceled)
5 . The method of claim 2 , wherein the cytoplasmic RNA virus is a coronavirus.
6 . (canceled)
7 . The method of claim 1 , wherein the RNA virus is a nuclear RNA virus selected from the group consisting of orthomyxovirus and retrovirus.
8 . (canceled)
9 . The method of claim 1 , wherein the agent that blocks a proviral function of the virus-derived circular RNA is selected from the group consisting of an siRNA, an shRNA, an RNA-targeting CRISPR-Cas system, and a small molecule.
10 . The method of claim 1 , wherein the agent that blocks a proviral function of the virus-derived circular RNA targets a back splicing or junction sequence of the virus-derived circular RNA.
11 . The method of claim 9 , wherein the agent that blocks a proviral function of the virus-derived circular RNA is an siRNA and wherein the siRNA comprises a nucleotide sequence of a junction sequence of the virus-derived circular RNA.
12 . The method of claim 9 , wherein the agent that blocks a proviral function of the virus-derived circular RNA is an siRNA and wherein the siRNA comprises a nucleotide sequence of a transcription regulatory sequence of the virus-derived circular RNA.
13 - 15 . (canceled)
16 . A method of promoting an innate immune response in a subject, the method comprising administering to the subject a virus-derived circular RNA derived from a genome of an RNA virus, wherein the virus-derived circular RNA promotes in the subject an innate immune response to the RNA virus.
17 . The method of claim 16 , wherein the virus-derived circular RNA is administered to the subject by a nanoparticle containing the virus-derived circular RNA or by a vector that encodes the virus-derived circular RNA.
18 . A method of promoting an innate immune response in a subject, the method comprising administering to the subject an agent that blocks a function of a virus-derived circular RNA derived from a genome of an RNA virus and wherein the virus-derived circular RNA reduces in the subject an innate immune response to the RNA virus.
19 . The method of claim 18 , wherein the agent that blocks a function of the virus-derived circular RNA is selected from the group consisting of an siRNA, an shRNA, a RNA-targeting CRISPR-Cas system, and a small molecule.
20 . (canceled)
21 . A method of treating an RNA viral infection in a subject, the method comprising:
(a) detecting in a biological sample from the subject a virus-derived circular RNA, wherein the virus-derived circular RNA is derived from a genome of an RNA virus; and
(b) administering to the subject a therapeutically effective amount of an antiviral agent.
22 . The method of claim 21 , wherein the antiviral agent is an agent that blocks a function of the virus-derived circular RNA and wherein the agent that blocks a function of the virus-derived circular RNA is selected from the group consisting of an siRNA, an shRNA, a RNA-targeting CRISPR-Cas system, and a small molecule.
23 . (canceled)
24 . A method of treating an RNA viral infection in a subject, comprising:
(a) detecting in a biological sample from the subject a polypeptide translated from a virus-derived circular RNA, wherein the virus-derived circular RNA is derived from a genome of a cytoplasmic RNA virus; and
(b) administering to the subject a therapeutically effective amount of an antiviral agent.
25 . The method of claim 24 , wherein the antiviral agent is an agent that blocks a function of the virus-derived circular RNA and wherein the agent that blocks a function of the virus-derived circular RNA is selected from the group consisting of an siRNA, an shRNA, a RNA-targeting CRISPR-Cas system, and a small molecule.
26 . (canceled)
27 . A nanoparticle comprising:
(a) an agent that blocks a function of a virus-derived circular RNA; and
(b) a polymer layer encapsulating the agent.
28 . The nanoparticle of claim 27 , wherein the agent that blocks a function of a virus-derived circular RNA is selected from the group consisting of an siRNA, an shRNA, a RNA-targeting CRISPR-Cas system, and a small molecule.
29 . The nanoparticle of claim 28 , wherein the siRNA, shRNA, or RNA-targeting CRISPR-Cas system or small molecule targets a back splicing junction of the virus-derived circular RNA.
30 . A vector encoding an siRNA, an shRNA, a RNA-targeting CRISPR-Cas system, or a small molecule that targets a virus-derived circular RNA, wherein the virus-derived circular RNA is derived from a genome of an RNA virus.
31 . A nanoparticle comprising:
(a) a vector encoding an siRNA, an shRNA, or a RNA-targeting CRISPR-Cas system that targets a virus-derived circular RNA, wherein the virus-derived circular RNA is derived from a genome of an RNA virus; and
(b) a polymer layer encapsulating the vector.
32 . A method of modulating an effect of a virus-derived circular RNA on one or more uninfected bystander cells, the method comprising contacting the one or more uninfected bystander cells with a therapeutically effective amount of an agent that blocks a proviral effect of the virus-derived circular RNA on the one or more uninfected bystander cells or an agent that promotes an antiviral effect of the virus-derived circular RNA in the one or more uninfected bystander cells.