Granted Patent
B2
US 12,509,701 · App. 18/544,160 · Granted Dec 30, 2025
Circular RNA for translation in eukaryotic cells
Inventors:
Daniel G. Anderson (Framingham, MA); Robert Alexander Wesselhoeft (Boston, MA); Piotr S. Kowalski (Cork, IE)
Assignee:
Massachusetts Institute of Technology
C12N15/85C07K16/2803C12N15/11C07K2317/31C12N2015/8518C12N2015/859C12N2800/107C12N2800/202C12N2800/70C12N2840/203C12N2840/55C12N2840/60C12N2999/007
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Abstract
Circular RNA and methods and constructs for engineering circular RNA are disclosed. In some embodiments, the circular RNA includes the following elements arranged in the following sequence: a) a 3′ Group I self-splicing intron fragment, b) an internal ribosome entry site (IRES), c) a protein coding region or noncoding region, and d) a 5′ Group I self-splicing intron fragment.
Claims (53)
1 . A circular RNA comprising the following elements arranged in the following sequence:
a) an exon sequence of a 3′ Group I self-splicing intron-exon,
b) a 5′ internal homology region,
c) an internal ribosome entry site (IRES),
d) a protein coding region,
e) a 3′ internal homology region, and
f) an exon sequence of a 5′ Group I self-splicing intron-exon,
wherein the 5′ internal homology region, the 3′ internal homology region, or both are exogenous to the Group I self-splicing intron-exon.
2 . The circular RNA of claim 1 , wherein the exon sequence of the 3′ Group I self-splicing intron-exon and the exon sequence of the 5′ Group I self-splicing intron-exon are from Cyanobacterium Anabaena or are from a Cyanobacterium Anabaena sp. pre-tRNA-Leu gene.
3 . The circular RNA of claim 1 , further comprising:
a) a 5′ spacer sequence comprising the 5′ internal homology region, and
b) a 3′ spacer sequence comprising the 3′ internal homology region.
4 . The circular RNA of claim 3 , wherein:
a) the 5′ spacer sequence is at least 7 nucleotides in length,
b) the 3′ spacer sequence is at least 7 nucleotides in length, or both a) and b).
5 . The circular RNA of claim 3 , wherein:
a) the 5′ spacer sequence is no more than 100 nucleotides in length,
b) the 3′ spacer sequence is no more than 100 nucleotides in length, or both a) and b).
6 . The circular RNA of claim 3 , wherein:
a) the 5′ spacer sequence is 10-60 nucleotides in length,
b) the 3′ spacer sequence is 10-60 nucleotides in length, or both a) and b).
7 . The circular RNA of claim 3 , wherein:
a) the 5′ spacer sequence comprises a polyA sequence, a polyC sequence, a polyA-C sequence, or a poly U sequence,
b) the 3′ spacer sequence comprises a polyA sequence, a polyC sequence, a polyA-C sequence, or a poly U sequence, or both a) and b).
8 . The circular RNA of claim 1 , wherein the IRES is selected from an IRES sequence of Taura syndrome virus, Triatoma virus, Theiler's encephalomyelitis virus, simian Virus 40, Solenopsis invicta virus 1, Rhopalosiphum padi virus, Reticuloendotheliosis virus, human poliovirus 1, Plautia stali intestine virus, Kashmir bee virus, Human rhinovirus 2, Homalodisca coagulata virus-1, Human Immunodeficiency Virus type 1, Homalodisca coagulata virus-1, Himetobi P virus, Hepatitis C virus, Hepatitis A virus, Hepatitis GB virus, foot and mouth disease virus, Human enterovirus 71, Equine rhinitis virus, Ectropis obliqua picorna-like virus, Encephalomyocarditis virus (EMCV), Drosophila C Virus, Crucifer tobamo pvirus, Cricket paralysis virus, Bovine viral diarrhea virus 1, Black Queen Cell Virus, Aphid lethal paralysis virus, Avian encephalomyelitis virus, Acute bee paralysis virus, Hibiscus chlorotic ringspot virus, Classical swine fever virus, Human FGF2, Human SFTPA1, Human AML1/RUNX1, Drosophila antennapedia , Human AQP4, Human ATIR, Human BAG-1, Human BCL2, Human BiP, Human c-IAP1, Human c-myc, Human eIF4G, Mouse NDST4L, Human LEF1, Mouse HIF1 alpha, Human n.myc, Mouse Gtx, Human p27kip1, Human PDGF2/c-sis, Human p53, Human Pim-1, Mouse Rbm3, Drosophila reaper, Canine Scamper, Drosophila Ubx, Salivirus, Cosavirus, Parechovirus, Human UNR, Mouse UtrA, Human VEGF-A, Human XIAP, Drosophila hairless, S. cerevisiae TFIID, S. cerevisiae YAP1, Human c-src, Human FGF-1, Simian picornavirus, Turnip crinkle virus, an aptamer to eIF4G, Coxsackievirus B3 (CVB3) or Coxsackievirus A (CVB1/2).
9 . The circular RNA of claim 1 , wherein the IRES is an IRES sequence from Coxscakievirus B3 (CBV3), Encephalomyocarditis virus (EMCV), or Salivirus.
10 . The circular RNA of claim 1 , wherein the circular RNA is at least 1,600 nucleotides in size.
11 . The circular RNA of claim 1 , wherein the circular RNA is at least 1,700 nucleotides in size.
12 . The circular RNA of claim 1 , wherein the protein coding region encodes a chimeric antigen receptor, a therapeutic protein, or a binding protein.
13 . The circular RNA of claim 1 , wherein the circular RNA is no more than 5,000 nucleotides in size.
14 . A composition, comprising:
a) an effective amount of a circular RNA, wherein the circular RNA comprises the following elements arranged in the following sequence:
i) an exon sequence of a 3′ Group I self-splicing intron-exon,
ii) a 5′ internal homology region,
iii) an internal ribosome entry site (IRES),
iv) a protein coding region,
v) 3′ internal homology region, and
vi) an exon sequence of a 5′ Group I self-splicing intron-exon, wherein the 5′ internal homology region, the 3′ internal homology region, or both are exogenous to the Group I self-splicing intron-exon; and
b) a nanocarrier selected from the group consisting of a lipid, a polymer and a lipo-polymeric hybrid.
15 . The composition of claim 14 , wherein the protein coding region encodes a chimeric antigen receptor, a therapeutic protein, or a binding protein.
16 . The composition of claim 14 , wherein the circular RNA is at least 1,600 nucleotides in size.
17 . The composition of claim 14 , wherein the circular RNA is at least 1,700 nucleotides in size.
18 . The composition of claim 14 , wherein the circular RNA is at least 2,000 nucleotides in size.
19 . The composition of claim 14 , wherein the circular RNA is no more than 5,000 nucleotides in size.
20 . A method of treating a disease, the method comprising administering an effective amount of a circular RNA to a subject in need thereof, wherein the circular RNA comprises the following elements arranged in the following sequence:
a) an exon sequence of a 3′ Group I self-splicing intron-exon,
b) a 5′ internal homology region,
c) an internal ribosome entry site (IRES),
d) a protein coding region,
e) a 3′ internal homology region, and
f) an exon sequence of a 5′ Group I self-splicing intron-exon,
wherein the 5′ internal homology region, the 3′ internal homology region, or both are exogenous to the Group I self-splicing intron-exon.
21 . The method of claim 20 , wherein the protein coding region encodes a chimeric antigen receptor, a therapeutic protein, or a binding protein.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 29, 2023
From: ANDERSON, DANIEL G.; WESSELHOEFT, ROBERT ALEXANDER; KOWALSKI, PIOTR S.
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 065980/0957 →
Continuity (9)
Provisional Application
62851548
· May 22, 2019
Provisional Application
62791028
· Jan 10, 2019
Provisional Application
62681617
· Jun 6, 2018
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