Nanovation Therapeutics Inc.

The University of British Columbia

Jayesh Kulkarni

Dominik Witzigmann

Daniel Kurek

Pieter Rutter Cullis

Blair Leavitt

Kevin An

Austin Hill

Pamela Wagner

Terri Petkau

Maunish Barvalia

Anthony Tam

The present disclosure provides a lipid nanoparticle comprising: a nucleic acid cargo molecule; sterol or a derivative thereof present at elevated content; neutral lipid; an ionizable lipid; and a hydrophilic polymer-lipid conjugate present at a content between 0.5 and 3 mol %, wherein each mol % content is relative to total lipid present in the lipid nanoparticle.

High sterol-containing lipid nanoparticles

The present disclosure provides unshielded lipid nanoparticles and a process that enables the production of such unshielded lipid nanoparticles, thereby overcoming previous challenges of making particles without causing aggregation thereof. The lipid nanoparticles comprise a nucleic acid cargo molecule; a sterol or a derivative thereof present at a content of at least 12 mol %; a neutral lipid, such as a phospholipid having a choline head group present at a content of between 22 mol % and 65 mol %; and an ionizable cationic amino lipid present at a content of between 15 mol % and 45 mol %; wherein the lipid nanoparticle is non-sterically stabilized with a hydrophilic polymer-lipid conjugate, or otherwise unshielded and wherein each mol % content is relative to total lipid present in the lipid nanoparticle.

Method of delivery of DNA or RNA cargo unshielded lipid nanoparticles and compositions thereof

The present disclosure provides a lipid nanoparticle for extrahepatic delivery of mRNA, the lipid nanoparticle comprising: (i) mRNA cargo; (ii) a phosphatidylcholine lipid content of from mol % to 70 mol %; (iii) a ionizable, cationic lipid content of from 5 mol % to 50 mol %; (iv) a sterol selected from cholesterol or a derivative thereof; and (v) a hydrophilic polymer-lipid conjugate that is present at a lipid content of 0.5 mol % to 5 mol. Further provided is a lipid nanoparticle preparation comprising lipid nanoparticles having encapsulated mRNA and 20 to mol % of a phosphatidylcholine lipid, an ionizable lipid; and at least one of a sterol and a hydrophilic polymer-lipid conjugate, the lipid nanoparticles exhibiting at least a 10% increase in gene expression of the mRNA in vivo as measured in one or more extrahepatic organs or tissues. The lipid nanoparticles have an electron dense region and a nitrogen-to-phosphate charge ratio of between 4 and 15.

MRNA delivery composition

Lipid-based vesicles, typically herein called transfection competent vesicles (TCVs), configured to safely and efficiently deliver DNA, RNA, other nucleic acid and protein cargoes into target cells. The safety and efficiency are each, and both, achieved in part by eliminating organic solvents such as ethanol and detergents such as sodium dodecyl sulfate from the TCV loading processes (i.e., inserting a cargo into the TCV), TCV storage processes, and/or TCV delivery processes. The cargoes can also comprise nucleic acids complexed with a protein, such as a ribonucleoprotein (RNP). The systems, compositions, devices and methods, etc., herein, in some embodiments, can provide empty TCVs that can if desired be loaded at the bench without use of specialized equipment.

Compositions and systems comprising transfection-competent vesicles free of organic-solvents and detergents and methods related thereto

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Vancouver, Canada

Jayesh Kulkarni