Encrypted RNA and Methods of Its Use
AssigneeAutonomous Therapeutics, Inc.
InventorsTimothy Notton, Andrii Kaberniuk, Anton Shemetov, Sayantan Bose, Mikhail Matlashov, Kristina Brazhnik, Ariel Weinberger, Won-Bin Young, Janice Ortega Rodríguez
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Abstract
Provided herein are encrypted RNAs, and DNAs that encode encrypted RNAs, that enable increased translation of polypeptides, including therapeutic polypeptides, after being contacted by translation activators, and methods of their use.
Claims251
An isolated RNA polynucleotide, comprising
- a coding region having a coding sequence encoding one or more therapeutic polypeptides;
- and
- template regions, wherein the template regions comprise two distinct regions, a left flanking region (“L region”) of a virus and a right flanking region (“R region”) of the virus, wherein the L region is adjacent to and contiguous with a 5′ end of the coding region and the R region is adjacent to and contiguous with a 3′ end of the coding region;
- wherein the coding sequence is in an antisense orientation;
- wherein the therapeutic polypeptide is heterologous to the virus;
- and
- wherein the template regions interact with and initiate RNA-dependent polymerase activity of a polymerase in a cell containing the RNA dependent polymerase.
An isolated RNA polynucleotide, comprising
- a coding region having a coding sequence encoding one or more polypeptide;
- and
- template regions, wherein the template regions comprise two distinct regions, a left flanking region (“L region”) of a virus and a right flanking region (“R region”) of the virus, wherein the L region is adjacent to and contiguous with a 5′ end of the coding region and the R region is adjacent to and contiguous with a 3′ end of the coding region;
- wherein the coding sequence is in a sense orientation;
- wherein the polypeptide is heterologous to the virus;
- wherein the template region interact with and initiate RNA-dependent polymerase activity of a polymerase in a cell containing the RNA dependent polymerase;
- and
- wherein the virus is not an alphavirus.
The isolated RNA polynucleotide of 126, wherein the template regions are nucleoside-modified and the percentage of modified nucleotides is not more than 40%, 35%, 30%, 25%, 20%, 15%, 10%, or 5%.
An isolated RNA polynucleotide, comprising
- a coding region having a coding sequence encoding one or more polypeptides;
- and
- template regions, wherein the template regions comprise two distinct regions, a left flanking region (“L region”) of a virus and a right flanking region (“R region”) of the virus, wherein the L region is adjacent to and contiguous with a 5′ end of the coding region and the R region is adjacent to and contiguous with a 3′ end of the coding region;
- wherein
- at least 30% of uridine nucleotides are modified,
- at least 30% of cytidine nucleotides are modified, and/or
- between 1-30% of adenosine nucleotides are modified;
- and
- wherein the template region interact with and initiate RNA-dependent polymerase activity of a polymerase in a cell containing the RNA dependent polymerase.
Dependencies are inferred from the claim text.