Granted Patent
B2
US 12,378,523 · App. 18/361,772 · Granted Aug 5, 2025
Platelets as delivery agents
Inventors:
Keith Andrew Moskowitz (Westfield, IN); Amber Nicole Lee (Montgomery Village, MD); Rafael Jorda (Merignac, FR)
Assignee:
Cellphire, Inc.
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Abstract
Provided herein are RNA agent-loaded platelets, methods of preparing RNA agent-loaded platelets, and methods of using RNA agent-loaded platelets. In some embodiments, methods of loading RNA agents into platelets include treating platelets with a RNA agent, a cationic transfection reagent, and a loading buffer that can include a salt, a base, a loading agent, and optionally at least one organic solvent.
Claims (26)
1. A method of preparing RNA agent-loaded cryopreserved platelets, comprising:
providing platelets;
treating the platelets with a RNA agent that is a siRNA and/or a miRNA in the presence of a cationic transfection reagent, and a loading buffer comprising a salt, a base, and a loading agent comprising one or more saccharides selected from the group consisting of trehalose, sucrose, maltose, mannose, dextrose, and xylose, for a time period in the range of 5 minutes to 4 hours, and at a temperature in the range of 18-42° C., to form RNA agent-loaded platelets; and
cryopreserving the RNA agent-loaded platelets in the presence of the loading buffer, dimethyl sulfoxide (DMSO), and polysucrose to form the RNA agent-loaded cryopreserved platelets,
wherein the RNA agent-loaded cryopreserved platelets after storage at a temperature of about −80° C., upon thawing:
retain at least 90% of the RNA agent, and
retain hemostatic function by displaying the property of occluding a capillary coated with collagen and tissue factor in an in vitro total thrombus-formation analysis system (T-TAS).
2. The method of claim 1 , wherein the platelets are pooled from a plurality of donors.
3. The method of claim 1 , wherein the loading buffer further comprises at least one organic solvent selected from the group consisting of ethanol, acetic acid, acetone, acetonitrile, dimethylformamide, dioxane, methanol, n-propanol, isopropanol, tetrahydrofuran (THF), N-methyl pyrrolidone, dimethylacetamide (DMAC), or combinations thereof.
4. The method of claim 1 , wherein the loading agent comprises dextrose, and trehalose, and DMSO is present in an amount in the range of 0.1% to 5.0% v/v.
5. The method of claim 4 , wherein the platelets are selected from the group consisting of fresh platelets, stored platelet, and any combination thereof.
6. The method of claim 4 , wherein the cationic transfection reagent is a cationic lipid transfection reagent.
7. The method of claim 6 , wherein the RNA agent comprises siRNA.
8. The method of claim 6 , wherein the RNA agent comprises miRNA.
9. The method of claim 1 , wherein the time period is in the range of 20 minutes to 3 hours, wherein the concentration of RNA agent in the RNA agent-loaded platelets is from about 0.1 nM to about 10 μM, and wherein the RNA agent-loaded cryopreserved platelets after storage, upon thawing retain at least 90% of channel occlusion in an in vitro total thrombus-formation analysis system (T-TAS).
10. The method of claim 9 , wherein the concentration of RNA agent in the RNA agent-loaded platelets is from about 10 nM to about 10 μM.
11. The method of claim 7 , wherein polysucrose is an amount in the range of 3% to 10% w/v, trehalose is in an amount in the range of 10 mM to 500 mM, DMSO is in an amount in the range of 0.3% to 3.0% v/v, and wherein the organic solvent comprises ethanol in an amount in the range of 0.1% to 5.0% v/v.
12. The method of claim 11 , wherein polysucrose is in an amount in the range of 3% to 7% w/v, and trehalose is in an amount in the range of 20 mM to 200 mM, and wherein DMSO is in an amount in the range of 0.5% to 2.0% v/v.
13. The method of claim 11 , wherein the RNA agent-loaded cryopreserved platelets are stored for at least 6 months.
14. The method of claim 8 , wherein polysucrose is in an amount in the range of 3% to 10% w/v, and trehalose is in an amount in the range of 10 mM to 500 mM, DMSO is in an amount in the range of 0.3% to 3.0% v/v, and wherein the at least one organic solvent comprises ethanol in an amount in the range of 0.1% to 5.0% v/v.
15. The method of claim 14 , wherein polysucrose is in an amount in the range of 3% to 7% w/v, and trehalose is in an amount in the range of 20 mM to 200 mM, and wherein DMSO is in an amount in the range of 0.5% to 2.0% v/v.
16. The method of claim 14 , wherein the RNA agent-loaded cryopreserved platelets are stored for at least 3 days, and wherein the RNA agent-loaded cryopreserved platelets after storage, upon thawing retain at least 90% of channel occlusion in an in vitro total thrombus-formation analysis system (T-TAS).
17. The method of claim 16 , wherein the RNA agent-loaded cryopreserved platelets are stored for at least 6 months.
18. The method of claim 16 , wherein the RNA agent-loaded cryopreserved platelets are stored for a time period of 3 days to 6 months.
19. The method of claim 14 , wherein the time period is in the range of 20 minutes to 3 hours, and the temperature in the range of 20° C. to 40° C.
20. The method of claim 11 , wherein the time period is in the range of 20 minutes to 3 hours, and the temperature in the range of 20° C. to 40° C., wherein the RNA agent-loaded cryopreserved platelets are stored for a time period of 3 days to 6 months, and wherein the RNA agent-loaded cryopreserved platelets after storage, upon thawing retain at least 90% of channel occlusion in an in vitro total thrombus-formation analysis system (T-TAS).
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 28, 2023
From: MOSKOWITZ, KEITH ANDREW; LEE, AMBER NICOLE; JORDA, RAFAEL
To: CELLPHIRE, INC.
Reel/Frame 064427/0391 →
Continuity (5)
Provisional Application
62828043
· Apr 2, 2019
Provisional Application
62775141
· Dec 4, 2018
Provisional Application
62773931
· Nov 30, 2018
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