Cns delivery of mrna and uses thereof
AssigneeTranslate Bio, Inc.
InventorsFrank DeRosa, Michael Heartlein, Shrirang Karve
Life of this patent
Estimating the term…
Abstract
The present invention provides, among other things, methods and compositions for effective delivery of messenger RNA (mRNA) to the central nervous system (CNS). In particular, the present invention provides methods and compositions for administering intrathecally to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome, such that the administering of the composition results in the intracellular delivery of mRNA in neurons in the brain and/or spinal cord. The present invention is particularly useful for the treatment of CNS diseases, disorders or conditions, such as spinal muscular atrophy.
Claims33
A method of delivery of messenger RNA (mRNA) to the central nervous system (CNS), comprising administering intrathecally to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome such that the administering of the composition results in the intracellular delivery of mRNA in neurons in the brain and/or spinal cord;
- wherein the liposome comprises cationic or non-cationic lipid, cholesterol-based lipid and PEG-modified lipid.
-4. (canceled)
-8. (canceled)
-12. (canceled)
-16. (canceled)
(canceled)
(canceled)
-29. (canceled)
(canceled)
-36. (canceled)
-39. (canceled)
A method of treating spinal muscular atrophy, comprising administering intrathecally to a subject in need of treatment a composition comprising an mRNA encoding the Survival of Motor Neuron (SMN) protein, encapsulated within a liposome such that the administering of the composition results in the intracellular delivery of mRNA in neurons in the brain and/or spinal cord;
- wherein the liposome comprises cationic or non-cationic lipid, cholesterol-based lipid and PEG-modified lipid.
-43. (canceled)
-49. (canceled)
A composition for treating spinal muscular atrophy, comprising an mRNA encoding the Survival of Motor Neuron (SMN) protein, encapsulated within a liposome;
- wherein the codon optimized mRNA comprises SEQ ID NO:3, SEQ ID NO:
- 4, SEQ ID NO:
- 10 or SEQ ID 0:11, and further wherein the liposome comprises cationic or non-cationic lipid, cholesterol-based lipid and PEG-modified lipid.
A composition for treating spinal muscular atrophy, comprising an mRNA encoding the Survival of Motor Neuron (SMN) protein, encapsulated within a liposome, wherein the liposome comprises a cationic lipid of formula I-c1-a:
- or a pharmaceutically acceptable salt thereof, wherein:
- each R2 independently is hydrogen or C1-3 alkyl;
- each q independently is 2 to 6;
- each R′ independently is hydrogen or Q
- and each RL independently is C8_12 alkyl
A composition for treating spinal muscular atrophy, comprising an mRNA encoding the Survival of Motor Neuron (SMN) protein, encapsulated within a liposome;
- wherein the liposome comprises a combination selected from
- C12-200, sphingomyelin, DOPE, Cholesterol, and DMG PEG;
- C12-200, DOPE, cholesterol and DMG-PEG2K;
- CKK-E12, DOPE, cholesterol and DMG-PEG2K;
- cKK-E12, sphingomyelin, DOPE, cholesterol and DMG-PEG2K;
- HGT5001, DOPE, cholesterol and DMG-PEG2K;
- HGT4003, DOPE, cholesterol and DMG-PEG2K;
- DLinKC2DMA, DOPE, cholesterol and DMG-PEG2;
- ICE, DOPE, cholesterol and DMG-PEG2K;
- DODMA, DOPE, cholesterol and DMG-PEG2K;
- or
- DODMA, sphingomyelin, DOPE, cholesterol and DMG-PEG2K.
Dependencies are inferred from the claim text.