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AssigneeFlagship Pioneering Innovations V, Inc.
InventorsAvak Kahvejian, Erica Gabrielle Weinstein, Roger Joseph Hajjar, Nathan Lawrence Yozwiak, Simon Delagrave, Yann Paul Guy Régis Echelard, Simeon Ungerleider Springer, Cesar A. Arze, Kristian Graugaard Andersen
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This invention relates generally to compositions and methods for administering an anellovector (e.g., a synthetic anellovector) that can be used as a delivery vehicle, e.g., for delivering genetic material, for delivering an effector, e.g., a payload, or for delivering a therapeutic agent or a therapeutic effector to a eukaryotic cell (e.g., a human cell or a human tissue). Also provided are methods for amplifying circular nucleic acids comprising Anellovirus sequences.
A method of delivering an exogenous effector to a human subject who has previously been administered a first plurality of anellovectors, said method comprising:
The method of any of the preceding claims, wherein the second plurality of anellovectors is administered to the subject at least 1, 2, 3, or 4 weeks, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months after the administration of the first plurality of anellovectors to the subject.
The method of any of the preceding claims, which further comprises administering to the subject a third, fourth, fifth, and/or further plurality of anellovectors comprising:
The method of any of the preceding claims, wherein the second plurality of anellovectors comprises comprises 90-110%, e.g., 95-105% of the number of anellovectors in the first plurality.
The method of any of the preceding claims, wherein the first plurality and the second plurality are administered via the same route of administration, e.g., intravenous administration.
The method of any of the preceding claims, wherein the second plurality of anellovectors comprises the same proteinaceous exterior as the anellovectors of the first plurality.
The method of any of the preceding claims, wherein the second plurality of anellovectors comprises an ORF1 molecule having the same amino acid sequence as the ORF1 molecule comprised by the anellovectors of the first plurality.
The method of any of the preceding claims, wherein the effector of the first plurality of anellovectors is an exogenous effector.
The method of any of the preceding claims, wherein the genetic element comprised in the anellovectors of the first plurality is detectable in the subject at least 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 days after administration thereof, e.g., by a high-resolution melting (HRM) assay.
The method of any of the preceding claims, wherein the genetic element comprised in the anellovectors of the second plurality is detectable in the subject at least 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 days after administration thereof, e.g., by a high-resolution melting (HRM) assay.
The method of any of the preceding claims, wherein the genetic element of the first and/or second plurality of anellovectors comprises an Anellovirus 5′ UTR (e.g., nucleotides 170-240 of SEQ ID NO:
The method of any of the preceding claims, wherein the genetic element of the first and/or second plurality of anellovectors comprises the nucleic acid sequence of nucleotides 323-393 of SEQ ID NO:
The method of any of the preceding claims, wherein the genetic element of the first and/or second plurality of anellovectors comprises a sequence of at least 100 nucleotides in length, which consists of G or C at at least 80% of the positions.
The method of any of the preceding claims, wherein the first and/or second plurality of anellovectors comprises a nucleic acid sequence encoding an amino acid sequence chosen from ORF1, ORF2, ORF2/2, ORF2/3, ORF1/1, or ORF1/2 of Table 12, or an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity thereto.
The method of any of the preceding claims, wherein the first and/or second plurality of anellovectors does not comprise a polypeptide having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to an Anellovirus ORF2, ORF2/2, ORF2/3, ORF1/1, or ORF1/2.
The method of any of the preceding claims, wherein the anellovectors of the first and/or second plurality are replication defective.
The method of any of the preceding claims, wherein the effector comprises:
A primer comprising a nucleic acid sequence according to any of SEQ ID NOs:
A mixture comprising a plurality of different primers comprising a nucleic acid sequence according to any 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or all of SEQ ID NOs:
A method of amplifying a circular DNA molecule comprising an Anellovirus sequence, the method comprising:
Dependencies are inferred from the claim text.