Delivery of large payloads
AssigneesThe Broad Institute, Inc., Massachusetts Institute of Technology, Trustees of Tufts College
InventorsFeng Zhang, Sourav Choudhury, Qiaobing Xu
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Abstract
The disclosure includes non-naturally occurring or engineered CRISPR systems and proteins, associated with a delivery system comprising a virus component and a lipid component. The disclosure includes CRISPR proteins associated with capsid proteins, e.g., AAV VP1VP2, and/or VP3, on the surface of or internal to the AAV, along with compositions, systems and complexes involving the AAV-CRISPR protein, nucleic acid molecules and vectors encoding the same, deliver}-systems, and uses therefor.
Claims31
A particle delivery system comprising a composite virus particle,
- wherein the composite virus particle comprises a lipid, at least a portion of a virus capsid protein, and at least a portion of a non-capsid protein or peptide, wherein the composite virus particle is adsorbed to a liposome comprising a targeting moiety,
- wherein the lipid is selected from EC16-63;
- 80-O14B;
- 80-O16B;
- 80-O18B;
- 87-O14B;
- 87-O16B;
- 87-O18B;
- 1-O18B:
- 80-O14;
- 80-O16;
- 80-O18;
- 87-O14;
- 87-O16;
- 87-O18;
- 1N16;
- 1-N18;
- 87-N17;
- 87-N16;
- 87-N18;
- EC 16-1;
- EC 16-3;
- EC16-12;
- EC16-14;
- and mixtures thereof.
A delivery system comprising one or more hybrid virus capsid proteins in combination with a lipid particle, wherein the one or more hybrid virus capsid proteins comprise at least a portion of a virus capsid protein attached to at least a portion of a non-capsid protein, wherein a virus particle is adsorbed to a liposome comprising a targeting moiety,
- wherein the lipid particle is selected from:
- EC16-63;
- 80-O14B;
- 80-O16B;
- 80-O18B;
- 87-O14B;
- 87-O16B;
- 87-O18B;
- 1-O18B;
- 80-O14;
- 80-O16;
- 80-O18;
- 87-O14;
- 87-O16;
- 87-O18;
- 1-N16;
- 1-N18;
- 87-N17;
- 87-N16;
- 87-N18;
- EC16-1;
- EC16-3;
- EC-16-12;
- EC16-14;
- and mixtures thereof.
A delivery system comprising a particle comprising a lipid layer, wherein a hybrid virus capsid protein comprising at least a portion of a virus capsid protein attached to a least a portion of a non-capsid protein is embedded in the lipid layer, wherein the virus capsid protein is adsorbed to a liposome comprising a targeting moiety,
- wherein the lipid particle is selected from:
- EC16-63;
- 80-O14B;
- 80-O16B;
- 80-O18B;
- 87-O14B;
- 87-O16B;
- 87-O18B;
- 1-O18B;
- 80-O14;
- 80-O16;
- 80-O18;
- 87-O14;
- 87-O16;
- 87-O18;
- 1-N16;
- 1-N18;
- 87-N17;
- 87-N16;
- 87-N18;
- EC16-1;
- EC16-3;
- EC-16-12;
- EC16-14;
- and mixtures thereof.
A particle delivery system comprising a hybrid protein that comprises a virus outer protein attached to at least a portion of a non-virus outer protein,
- wherein the hybrid protein is a hybrid virus capsid protein or hybrid viral outer protein coat or hybrid envelope protein, the virus outer protein is a virus capsid or outer protein coat or envelope protein and the non-virus outer protein is a protein that is not a virus outer coat protein, wherein the virus outer protein is adsorbed to a liposome comprising a targeting moiety,
- wherein the lipid particle is selected from:
- EC16-63;
- 80-O14B;
- 80-O16B;
- 80-O18B;
- 87-O14B;
- 87-O16B;
- 87-O18B;
- 1-O18B;
- 80-O14;
- 80-O16;
- 80-O18;
- 87-O14;
- 87-O16;
- 87-O18;
- 1-N16;
- 1-N18;
- 87-N17;
- 87-N16;
- 87-N18;
- EC16-1;
- EC16-3;
- EC-16-12;
- EC16-14;
- and mixtures thereof.
A virus particle comprising one or more hybrid virus capsid protein or one or more hybrid virus outer protein, wherein the one or more hybrid virus capsid proteins comprise a virus capsid protein attached to a non-capsid protein or a CRISPR protein, and the hybrid outer virus protein comprises a virus outer protein attached to a non-virus outer protein or a CRISPR protein, wherein the virus particle is adsorbed to a liposome comprising a targeting moiety,
- wherein the lipid particle is selected from:
- EC16-63;
- 80-O14B;
- 80-O16B;
- 80-O18B;
- 87-O14B;
- 87-O16B;
- 87-O18B;
- 1-O18B;
- 80-O14;
- 80-O16;
- 80-O18;
- 87-O14;
- 87-O16;
- 87-O18;
- 1-N16;
- 1-N18;
- 87-N17;
- 87-N16;
- 87-N18;
- EC16-1;
- EC16-3;
- EC-16-12;
- EC16-14;
- and mixtures thereof.
Dependencies are inferred from the claim text.