Research Summary

My major research contributions are to the treatment of disease, notably cancer and its complications, using liposomal nanoparticle (LNP) drug delivery systems. These contributions include early work that led to two drugs that have been approved for clinical use by regulatory authorities in the United States and Europe. Subsequent efforts within Inex Pharmaceuticals, a biotechnology company that I co-founded in 1992 (I was Vice President, Research at Inex from 1992 to 2004; 50% time) have led to three drugs that are in the clinic. Finally, I am currently focused on developing optimized LNP systems for the in vivo delivery of siRNA for gene silencing applications.

Spin-Offs

Canadian Liposome Company, Northern Lipids, Lipex Biomembranes, Synapse Technologies, Protiva Biotherapeutics, Inex Pharmaceuticals Corp (now Tekmira Pharmaceuticals), AlCana Technolgoies, Precision NanoSystems, Mesentech

Intellectual Property

1. Methods and compositions for delivery of nucleic acids – Inter Application No.:PCT/US2010/061058, United States, Washington
Filing Date: 2010-12-17

2. Reverse head group lipids, lipid particle compositions comprising reverse headgroup lipids, and methods for the delivery of nucleic acids – PCT/US2010/054351, United States, Washington
Filing Date: 2010-10-27

3. Improved amino lipids and methods for the delivery of nucleic acids – Application Number: 09819991, Canada, British Columbia
Filing Date: 2009-10-09

4. Lipid-encapsulated polyanionic nucleic acid – 8,021,686, United States, Maryland
Filing Date: 2008-02-08

5. Liposomal formulations comprising dihydrosphingomyelin and methods of use thereof – 7,811,602, United States, Maryland
Filing Date: 2005-05-16

6. Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer – 7,422,902, United States, Maryland
Filing Date: 1999-11-01

7. Triggered release of liposomal drugs following mixing of cationic and anionic liposomes – 7,273,620, United States, Maryland
Filing Date: 2003-05-19

8. Methods of enhancing SPLP-mediated transfection using endosomal membrane destabilizers – 7,189,705, United States, Maryland
Filing Date: 2001-04-20

9. Methods for preparation of lipid-encapsulated therapeutic agents – 7,094,423, United States, Maryland
Filing Date: 2000-07-14

10. Cationic peg-lipids and methods of use – 6,852,334, United States, Maryland
Filing Date: 2000-04-20

11. Composition containing small multilamellar oligodeoxynucleotide-containing lipid vesicles – 6,835,395, United States, Maryland
Filing Date: 2000-09-01

12. Methods for encapsulating plasmids in lipid bilayers – 6,815,432, United States, Maryland
Filing Date: 2003-02-24

13. Methods and compositions using liposome-encapsulated non-steroidal anti- inflammatory drugs – 6,759,057, United States, Maryland
Filing Date: 1989-03-13

14. Methods for encapsulating nucleic acids in lipid bilayers – 6,734,171, United States, Maryland
Filing Date: 1998-10-09

15. Liposome having an exchangeable component – 6,673,364, United States, Maryland
Filing Date: 1998-06-12

16. Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer – 6,586,410, United States, Maryland
Filing Date: 2000-05-08

17. Methods for encapsulating plasmids in lipid bilayers – 6,534,484, United States, Maryland,
Filing Date: 1999-11-08

18. Fusogenic liposomes – 6,417,326, United States, Maryland
Filing Date: 1997-04-10

19. Methods of preparing low-toxicity drug-lipid complexes – 6,406,713, United States, Maryland
Filing Date: 1995-04-28

20. High drug:lipid formulations of liposomal-antineoplastic agents – 6,083,530, United States, Maryland
Filing Date: 1998-05-26

21. Methods for encapsulating plasmids in lipid bilayers – 5,981,501, United States, Maryland
Filing Date: 1995-06-07

22. Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer – 5,976,567, United States, Maryland
Filing Date: 1996-06-06

23. Methods of dehydrating, storing and rehydrating liposomes – 5,922,350, United States, Maryland
Filing Date: 1997-06-16

24. Bilayer stabilizing components and their use in forming programmable fusogenic liposomes – 5,885,613, United States, Maryland
Filing Date: 1995-06-07

25. Ionophore-mediated liposome loading – 5,837,282, United States, Maryland
Filing Date: 1996-10-30

26. Encapsulation of ionizable agents in liposomes – 5,837,279, United States, Maryland
Filing Date: 1995-05-25

27. Liposomal antineoplastic agent compositions – 5,795,589, United States, Maryland
Filing Date: 1997-02-05

28. Methods for increasing the circulation half-life of protein-based therapeutics – 5,780,054, United States, Maryland
Filing Date: 1996-01-17

29. Methods of treatment using high drug-lipid formulations of liposomal- antineoplastic agents – 5,744,158, United States, Maryland
Filing Date: 1995-05-25

30. Encapsulation of antineoplastic agents in liposomes – 5,736,155, United States, Maryland
Filing Date: 1995-06-05

31. Low toxicity drug-lipid systems – 5,616,334, United States, Maryland
Filing Date: 1995-04-28

32. High drug:lipid formulations of liposomal antineoplastic agents – 5,616,341, United States, Maryland
Filing Date: 1993-08-26

33. Liposomal compositions for enhanced retention of bioactive agents – 5,595,756, United States, Maryland
Filing Date: 1993-12-02

34. Method of dehydrating liposomes using protective sugars – 5,578,320, United States, Maryland
Filing Date: 1993-02-24

35. Fusogenic lipsomes and methods for making and using same – 5,552,155, United States, Maryland
Filing Date: 1994-08-15

36. Method for entrapment of cationic species in lemellar vesicles – 5,525,232, United States, Maryland Filing Date: 1993-10-14

37. Liposomes comprising aminoglycoside phosphates and methods of production and use (expired) – 5,409,704, United States, Maryland
Filing Date: 1993-05-06

38. Accumulations of amino acids and peptides into liposomes – 5,380,531, United States, Maryland
Filing Date: 1992-06-02

39. Composition for targeting, storing and loading of liposomes – 5,171,578, United States, Maryland
Filing Date: 1991-06-06

40. Preparation of targeted liposome systems of a defined size distribution (expired) – 5,059,421, United States, Maryland
Filing Date: 1989-06-23

Bio

Bachelors of Science – Physics – University of British Columbia
Doctor of Philosophy in Science – Physics – University of British Columbia
Post-doctorate – Postdoctoral Fellow of the Medical Research Council – Biochemistry – Oxford University, U.K.
Post-doctorate – Fellow of the European Molecular Biology Organization – Biochemistry – Utrecht University

Publications

 
Comprehensive List
Google Scholar

Selected Publications

1. Neumann, UH., et al., IGFBP2 Is Neither Sufficient nor Necessary for the Physiological Actions of Leptin on Glucose Homeostasis in Male ob/ob Mice. Endocrinology, 155(3):716-25 (2014)

2. Walsh C., et al., Microfluidic-Based Manufacture of siRNA-Lipid Nanoparticles for Therapeutic Applications. Methods Mol Biol., 1141:109-20 (2014)

3. Tam YYC., et al., Advances in Lipid Nanoparticles for siRNA Delivery. Pharmaceutics, 5(3):498-507 (2013)

4. Mui BL., et al., Influence of Polyethylene Glycol Lipid Desorption Rates on Pharmacokinetics and Pharmacodynamics of siRNA Lipid Nanoparticles. Mol Ther Nucleic Acids., Dec 17;2:e139 (2013)

5. Tam, YYC., et al., Small molecule ligands for enhanced intracellular delivery of lipid nanoparticle formulations of siRNA. Nanomedicine, Jul;9(5):665-74 (2013)

6. Allen, TM. & Cullis, PR., Liposomal drug delivery systems: from concept to clinical applications. Advanced drug delivery reviews, 65:36-48, (2013)

7. Maier, MA., et al., Biodegradable Lipids Enabling Rapidly Eliminated Lipid Nanoparticles for Systemic Delivery of RNAi Therapeutics. Mol Ther., Aug;21(8):1570-8 (2013)

8. Lin, PJC., et al., Influence Of Cationic Lipid Composition On Uptake And Intracellular Processing Of Lipid Nanoparticle Formulations Of siRNA In A Macrophage Cell Line. Nanomedicine, 9:233-246 (2013)

9. Rungta, RL., et al., Lipid Nanoparticle Delivery of siRNA to Silence Gene Expression in the Brain. Mol Ther Nucleic Acids, Dec 3;2:e136 (2013)

10. Novobrantseva, TI. et al., Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells. Mol Ther Nucleic Acids, Jan 24;1:e4 (2012)

11. Jayaraman M., et al., Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo. Angew Chem Int Ed Engl, Aug 20;51(34):8529-33 (2012)

12. Zhigaltsev, IV., et al., Bottom-up design and synthesis of limit size lipid nanoparticle systems with aqueous and triglyceride cores using millisecond microfluidic mixing. Langmuir : the ACS journal of surfaces and colloids, 28:3633-3640 (2012)

13. Belliveau, NM., et al., Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for In Vivo Delivery of siRNA. Molecular therapy. Nucleic acids 1:e37 (2012)

14. Lee, J B., et al., Lipid nanoparticle siRNA systems for silencing the androgen receptor in human prostate cancer in vivo. International journal of cancer. Journal international du cancer, 131:E781-790 (2012)

15. Leung, AK., et al., Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core. The journal of physical chemistry, nanomaterials and interfaces, 116:18440-18450 (2012)

16. Basha, G., et al., Influence of cationic lipid composition on gene silencing properties of lipid nanoparticle formulations of siRNA in antigen-presenting cells. Molecular therapy, 19: 2186-2200 (2011)

17. Geetha-Loganathan, P., et al., Development of high-concentration lipoplexes for in vivo gene function studies in vertebrate embryos. Dev Dyn, Sep 240;(9):2108-19 (2011)

18. Zhigaltsev, IV., et al., Development of a weak-base docetaxel derivative that can be loaded into lipid nanoparticles. Journal of controlled release: official journal of the Controlled Release Society, 144:332-340 (2010)

19. Semple, S.,et al., Rational design of cationic lipids for siRNA delivery. Nature biotech, 28:172-176 (2010)

Additional Lists

http://www.ncbi.nlm.nih.gov/pubmed?term=Cullis%20PR%5BAuthor%5D&cauthor=true&cauthor_uid=24301867

Also see www.liposomes.ca/publications.php

Office Phone
6048270347
Office
1352