Methods and models for rapid, widespread delivery of genetic material to the CNS using non-viral, cationic lipid-mediated vectors

摘要

Provided are safe, non-invasive, non-viral delivery methods for providing a nucleic acid into the neuronal and non-neuronal cells of the central nervous system (CNS) of a subject to protect neuronal and non-neuronal cells from ischemic or traumatic injury, wherein the nucleic acid encodes a therapeutic proteins, specifically providing rapid transient expression and widespread distribution for in vitro or in vivo applications. Further provided are methods for the intrathecal delivery to the cerebrospinal fluid (CSF) of a neuroprotective gene sequence, e.g., a heat shock protein (HSP), complexed with cationic lipid compositions to achieve such delivery, and the complexes used therein.

主权项

1. A method for non-viral delivery of a nucleic acid into the neuronal and non-neuronal cells of the central nervous system (CNS) of a subject to protect neuronal and non-neuronal cells from ischemic or traumatic injury, wherein the nucleic acid encodes a mono- or poly-peptide when operably-linked to a promoter, the method comprising:
complexing the nucleic acid encoding a mono- or polypeptide when operably-linked to a promoter with a cationic, lipid congener to form a lipid-based nucleic acid lipoplex or vector to protect and stabilize the nucleic acid; and intrathecally administering the lipoplex to the cerebrospinal fluid (CSF) of the subject to deliver the protected, stable and active nucleic acid to the neuronal and non-neuronal cells of the CNS of the subject, wherein the subject is a primate or a human; and wherein the copy number of the nucleic acid in the neuronal and non-neuronal cells of the CNS is at least 5-fold higher than in cells outside the CNS.