Compositions and methods for therapeutic delivery with microorganisms

• US 8,852,916 B2
• Filed: 01/22/2010
• Issued: 10/07/2014
• Est. Priority Date: 01/22/2010
• Status: Expired due to Fees

• Current Assignee: Gearbox LLC (Intellectual Ventures LLC)
• Original Assignee: The Invention Science Fund I, L.L.C. (Intellectual Ventures LLC)
• Inventors: Hyde, Roderick A., Jung, Edward K. Y., Levien, Royce A., Lord, Robert W., Malamud, Mark A., Rinaldo, John D. Jr., Wood, Lowell L. Jr.
• Primary Examiner(s): Gussow, Anne
• Assistant Examiner(s): Mahatan, Channing S
• Application Number:
  US12/657,607
• Publication Number:
  US 20110183347A1
• Time in Patent Office: 1,719 Days
• Field of Search: None
• US Class Current: 435/252.3
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 35/747 Lactobacilli, e.g. L. acidophilus or L. brevis
• CPC Class Codes: A61K 36/064 Saccharomycetales, e.g. baker's yeast
• CPC Class Codes: A61K 38/162 from virus
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/2013 IL-2
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 38/208 IL-12
• CPC Class Codes: C12N 1/36 Adaptation or attenuation of cells
• CPC Class Codes: C12N 15/635 Externally inducible repressor mediated regulation of gene expression, e.g. tetR inducible by tetracyline
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Certain embodiments disclosed relate to compositions, including therapeutic compositions, methods, devices, and systems that include modified microorganisms including at least one genetic element encoding at least one therapeutic agent or environmental treatment agent.

Claims

1. A composition, comprising:

at least two modified microorganisms that are mutually dependent and express at least one environmental medium treatment agent only after satisfying a population threshold, at least one modified microorganism including at least one heterologous genetic element encoding at least one-environmental medium treatment agent including at least one of nitroreductase; and

at least one modified microorganism including at least one heterologous genetic element encoding at least one environmental medium treatment agent including an enzyme required to produce at least one plant growth factor;

and wherein each of the at least two modified microorganisms include

at least one genetic element operably coupled to at least one promoter or enhancer and inducible to initiate death of the at least one modified microorganism; and

at least one sensor including an RNA aptamer, a hammerhead ribozyme actuator, and a transmitter including a sequence that couples the sensor and actuator.

2. The composition of claim 1, wherein the at least one genetic element inducible to initiate death of the at least two modified microorganisms includes at least one heterologous genetic element.

3. The composition of claim 1, wherein the at least one plant growth factor includes at least one plant hormone.

4. The composition of claim 3, wherein the at least one plant hormone includes at least one of an auxin, abscisic acid, cytokinin, ethylene, gibberellin, brassinolide, salicyclic acid, jasmonate, polyamine, plant peptide hormone, nitric oxide, or strigolactone.

5. The composition of claim 1, wherein the at least one genetic element inducible to initiate death of the at least two modified microorganisms includes at least one of an inducible promoter, inducible enhancer, or inducible repressor.

6. The composition of claim 1, further including at least one metabolite utilizable by at least one of the at least two modified microorganisms.

7. The composition of claim 6, wherein the at least one metabolite includes at least one inducer of the heterologous genetic element encoding at least one environmental medium treatment agent.

8. The composition of claim 6, wherein the at least one metabolite includes at least one repressor of at least one of the heterologous genetic elements encoding at least one environmental medium treatment agent.

9. The composition of claim 6, wherein the at least one metabolite includes at least one inducer of at least one genetic element inducible to initiate death of at least one of the two modified microorganisms.

10. The composition of claim 6, wherein the at least one metabolite includes at least one repressor of the at least one genetic element inducible to initiate death of at least one of the two modified microorganisms.

11. The composition of claim 6, wherein the at least one metabolite includes a time-release formulation.

12. The composition of claim 6, wherein the at least one metabolite is pH-dependent.

13. The composition of claim 6, wherein the at least metabolite is temperature dependent.

14. The composition of claim 6, wherein the at least one metabolite includes the at least one environmental medium treatment agent.

15. The composition of claim 6, wherein the at least one metabolite is provided or produced by the at least one environmental medium.

16. The composition of claim 6, wherein the at least one metabolite is provided by at least one biological cell.

17. The composition of claim 1, wherein the at least one genetic element inducible to initiate death of either of the modified microorganisms includes at least one genetic element inducible to initiate programmed cell death.

18. The composition of claim 1, wherein the at least one modified microorganism includes at least one of a prokaryote or a eukaryote.

19. The composition of claim 1, wherein the at least one modified microorganism includes at least one of bacteria, protozoa, rotifers, algae, archaeon, or fungi.

20. The composition of claim 1, wherein the at least one modified microorganism includes at least one of a non-pathogenic strain, transgenic microorganism, magnetotactic microorganism, anaerobic microorganism or aerobic microorganism, food grade strain, obligate microorganism, attenuated microorganism strain, facultative anaerobe, non-invasive strain, probiotic, colonizing microorganism, element-modifying microorganism, photosynthetic microorganism.

21. The composition of claim 20, wherein the at least one element-modifying microorganism includes at least one of a nitrogen-fixing microorganism, nitrifying microorganism, denitrifying microorganism, hydrocarbon-utilizing microorganism, dechlorinating microorganism, or a sulfate-reducing microorganism.

22. The composition of claim 1, wherein the at least one environmental medium treatment agent is pH dependent.

23. The composition of claim 1, wherein the composition includes at least one time-release formulation.

24. The composition of claim 23, wherein the time-release formulation includes at least one of a suspension, mixture, solution, sol, clathrate, colloid, emulsion, microemulsion, aerosol, ointment, capsule, micro-encapsule, cream, paste, resin, liniment, lotion, foam, polymer, buffer, lubricant, suspending agent, solvent, stabilizer, or gel.

25. The composition of claim 1, wherein the at least one environmental medium treatment agent is encoded by at least one vector.

26. The composition of claim 1, further including at least one detection material associated with each of the at least two modified microorganisms.

27. The composition of claim 26, wherein the at least one detection material includes at least one, sensor, contrast agent, or electronic identification device.

28. The composition of claim 27, wherein the at least one sensor includes at least one biosensor.

29. The composition of claim 27, wherein the at least one electronic identification device includes at least one radio frequency identification device.

30. The composition of claim 26, wherein the at least one detection material includes at least one of a radioactive, luminescent, colorimetric or odorous substance.

31. The composition of claim 26, wherein the detection material includes at least one of a diamagnetic particle, ferromagnetic particle, paramagnetic particle, super paramagnetic particle, particle with altered isotope, or other magnetic particle.

32. The composition of claim 26, wherein the detection material includes at least one of a DNA or RNA device.

33. The composition of claim 26, wherein the detection material or a precursor thereof is encoded by the at least one heterologous genetic element encoding at least one environmental medium treatment agent.

34. The composition of claim 26, wherein the detection material includes the at least one environmental medium treatment agent or a metabolite thereof.