COMPOSITIONS AND METHODS TO MODIFY CELLS FOR THERAPEUTIC OBJECTIVES
First Claim
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1. A synthetic nanocarrier comprising (i) a lipid-coated porous nanoparticle (ii) a lymphocyte-directing agent extending from the surface of the lipid-coated porous nanoparticle;
- and (iii) a polynucleotide encoding a chimeric antigen receptor (CAR) targeting agent within the pores of the lipid-coated porous nanoparticle.
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Abstract
The present disclosure provides compositions and methods that rapidly and selectively modify cells of the immune system to achieve therapeutic objectives. The methods can be practiced in vivo and any cell type that expresses a known marker can be targeted for a therapeutic objective.
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Citations
42 Claims
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1. A synthetic nanocarrier comprising (i) a lipid-coated porous nanoparticle (ii) a lymphocyte-directing agent extending from the surface of the lipid-coated porous nanoparticle;
- and (iii) a polynucleotide encoding a chimeric antigen receptor (CAR) targeting agent within the pores of the lipid-coated porous nanoparticle.
- View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 27, 28, 29, 30)
- 2. A synthetic nanocarrier of embodiment 1 further comprising an endosomal release agent extending from the surface of the lipid-coated porous nanoparticle and (ii) a nuclear localization signal (NLS) within the pores of the lipid-coated porous nanoparticle.
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31. A method for treating a disease associated with an antigen, the method comprising:
- administering to a subject in need thereof, a composition comprising a therapeutically effective amount of nanocarriers including a polynucleotide having a sequence that encodes a receptor for the antigen, thereby treating the disease.
- View Dependent Claims (32)
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33. A method for treating a disease associated with an antigen, the method comprising:
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obtaining lymphocytes from a subject in need thereof; combining the lymphocytes with a composition comprising nanocarriers including a polynucleotide having a sequence that encodes a receptor for the antigen, wherein the nanocarriers are selectively incorporated into the lymphocytes such that the lymphocytes express the receptor; and administering the lymphocytes expressing the receptor to the subject, thereby treating the disease. - View Dependent Claims (34)
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35. A method of selectively transfecting lymphocytes in vivo, the method comprising:
contacting lymphocytes with nanocarriers comprising a polynucleotide having a sequence that encodes a receptor for an antigen associated with a disease, wherein the nanocarriers are selectively incorporated into the lymphocyte to release the polynucleotide such that the lymphocyte expresses the receptor, thereby transfecting the lymphocyte. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42)
Specification