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公开(公告)号:US11981909B2
公开(公告)日:2024-05-14
申请号:US16432177
申请日:2019-06-05
Applicant: Massachusetts Institute of Technology
Inventor: Daniel G. Anderson , Robert Alexander Wesselhoeft , Piotr S. Kowalski
CPC classification number: C12N15/85 , C07K16/2803 , C12N15/11 , C07K2317/31 , C12N2015/8518 , C12N2015/859 , C12N2800/107 , C12N2800/202 , C12N2800/70 , C12N2840/203 , C12N2840/55 , C12N2840/60 , C12N2999/007
Abstract: Disclosed are methods and constructs for engineering circular RNA Disclosed is a vector for making circular RNA, said vector comprising the following elements operably connected to each other and arranged in the following sequence: a) a 5′ homology arm, b) a 3′ group I intron fragment containing a 3′ splice site dinucleotide, c) an optional 5′ spacer sequence, d) a protein coding or noncoding region, e) an optional 3′ spacer sequence, f) a 5′ Group I intron fragment containing a 5′ splice site dinucleotide, and g) a 3′ homology arm. This vector allows production of a circular RNA that is translatable or biologically active inside eukaryotic cells. In one embodiment, the vector can comprise the 5′ spacer sequence, but not the 3′ spacer sequence. In yet another embodiment, the vector can also comprise the 3′ spacer sequence, but not the 5′ spacer sequence.
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公开(公告)号:US20230331806A1
公开(公告)日:2023-10-19
申请号:US18069621
申请日:2022-12-21
Inventor: Robert Alexander Wesselhoeft , Daniel G. Anderson , Shinichiro Fuse , Brian Goodman , Allen T. Horhota , Raffaella Squilloni
IPC: C07K14/725 , A61K9/51 , A61K35/17 , C07K16/28
CPC classification number: C07K14/7051 , A61K9/51 , A61K35/17 , C07K16/28 , A61K38/00
Abstract: Circular RNA and transfer vehicles, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes a chimeric antigen receptor (CAR). In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.
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公开(公告)号:US11603396B2
公开(公告)日:2023-03-14
申请号:US17548247
申请日:2021-12-10
Inventor: Robert Alexander Wesselhoeft , Daniel G. Anderson , Shinichiro Fuse , Brian Goodman , Allen T. Horhota , Raffaella Squilloni
Abstract: Circular RNA and transfer vehicles, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes a chimeric antigen receptor (CAR). In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.
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公开(公告)号:US20220177540A1
公开(公告)日:2022-06-09
申请号:US17548247
申请日:2021-12-10
Inventor: Alexander Wesselhoeft , Daniel G. Anderson , Shinichiro Fuse , Brian Goodman , Allen T. Horhota , Raffaella Squilloni
IPC: C07K14/725 , A61K9/51 , A61K35/17 , C07K16/28
Abstract: Circular RNA and transfer vehicles, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes a chimeric antigen receptor (CAR). In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.
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公开(公告)号:US20210403944A1
公开(公告)日:2021-12-30
申请号:US17468100
申请日:2021-09-07
Applicant: Massachusetts Institute of Technology
Inventor: Daniel G. Anderson , Robert Alexander Wesselhoeft , Piotr S. Kowalski
Abstract: Methods and constructs for engineering circular RNA are disclosed. In some embodiments, the methods and constructs comprise a vector for making circular RNA, the vector comprising the following elements operably connected to each other and arranged in the following sequence: a.) a 5′ homology arm, b.) a 3′ group I intron fragment containing a 3′ splice site dinucleotide, c.) optionally, a 5′ spacer sequence, d.) a protein coding or noncoding region, e.) optionally, a 3′ spacer sequence, f) a 5′ Group I intron fragment containing a 5′ splice site dinucleotide, and g.) a 3′ homology arm, the vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. Methods for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector are also disclosed.
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公开(公告)号:US11203767B2
公开(公告)日:2021-12-21
申请号:US17191697
申请日:2021-03-03
Applicant: Massachusetts Institute of Technology
Inventor: Daniel G. Anderson , Robert Alexander Wesselhoeft , Piotr S. Kowalski
Abstract: Methods and constructs for engineering circular RNA are disclosed. In some embodiments, the methods and constructs comprise a vector for making circular RNA, the vector comprising the following elements operably connected to each other and arranged in the following sequence: a.) a 5′ homology arm, b.) a 3′ group I intron fragment containing a 3′ splice site dinucleotide, c.) optionally, a 5′ spacer sequence, d.) a protein coding or noncoding region, e.) optionally, a 3′ spacer sequence, f.) a 5′ Group I intron fragment containing a 5′ splice site dinucleotide, and g.) a 3′ homology arm, the vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. Methods for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector are also disclosed.
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公开(公告)号:US20210353781A1
公开(公告)日:2021-11-18
申请号:US17278383
申请日:2019-09-23
Inventor: Omid Veiseh , Volkan Yesilyurt , Andrew Bader , Whitney Loo , Daniel G. Anderson , Robert S. Langer
Abstract: Surface-modified cell containing a cell and a conformal coating on the extracellular surface of the cell are described. The conformal coating contains two or more layers containing particles (e.g. nanoparticles) or macromolecules. The cell is an islet cell, a B cell, or a T cell. The macromolecules or particles are formed from zwitterionic polymers. Covalent linkages are employed to link the particles or macromolecules to a cell surface molecule containing an abiotic functional group, or between macromolecules and/or particles in adjacent layers. Also described are methods of making and using a surface-modified cell.
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公开(公告)号:US20210324370A1
公开(公告)日:2021-10-21
申请号:US17195625
申请日:2021-03-08
Applicant: Massachusetts Institute of Technology
Inventor: Hao Yin , Wen Xue , Daniel G. Anderson , Joseph R. Dorkin , Tyler E. Jacks
Abstract: The present disclosure relates to compositions and methods for modifying a gene sequence, and for systems for deliverying such compositions. For example, the disclosure relates to modifying a gene sequence using a CRISPR-Cas9 or other nucleic acid editing system, and methods and delivery systems for achieving such gene modification, such as viral or non-viral delivery systems.
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公开(公告)号:US20210198688A1
公开(公告)日:2021-07-01
申请号:US17191697
申请日:2021-03-03
Applicant: Massachusetts Institute of Technology
Inventor: Daniel G. Anderson , Robert Alexander Wesselhoeft , Piotr S. Kowalski
Abstract: Disclosed are methods and constructs for engineering circular RNA. Disclosed is a vector for making circular RNA, said vector comprising the following elements operably connected to each other and arranged in the following sequence:
a.) a 5′ homology arm, b.) a 3′ group I intron fragment containing a 3′ splice site dinucleotide, c.) optionally, a 5′ spacer sequence, d.) a protein coding or noncoding region, e.) optionally, a 3′ spacer sequence, f) a 5′ Group I intron fragment containing a 5′ splice site dinucleotide, and g.) a 3′ homology arm, said vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. In another embodiment, the vector can comprise the 5′ spacer sequence, but not the 3′ spacer sequence. In yet another embodiment, the vector can comprise the 3′ spacer sequence, but not the 5′ spacer sequence. Also disclosed is a method for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector.-
公开(公告)号:US20210186886A1
公开(公告)日:2021-06-24
申请号:US17080355
申请日:2020-10-26
Inventor: Arturo J. Vegas , Minglin Ma , Kaitlin M. Bratlie , Daniel G. Anderson , Robert S. Langer
Abstract: Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for the encapsulation and transplantation of cells. Also disclosed are high throughput methods for the characterizing the biocompatibility and physiochemical properties of modified alginate polymers.
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