Viral vectors for treating Parkinson's disease
Inventors
Lahusen, Tyler • Pauza, Charles David
Assignees
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Publication Number
US-11583562-B2
Publication Date
2023-02-21
Expiration Date
Abstract
A lentiviral vector system for expressing a lentiviral particle is disclosed. The lentiviral vector system includes a therapeutic vector, an envelope plasmid, and at least one helper plasmid. The lentiviral vector system can produce a lentiviral particle for inhibiting PARP expression in neuron cells of a subject afflicted with Parkinson's disease.
Core Innovation
The invention relates to a lentiviral vector system for treating Parkinson’s disease in a patient in need thereof. The system includes a therapeutic vector comprising an encoded shRNA for inhibiting PARP1 expression in neurons, with at least 80% sequence identity to the entire length of any one of SEQ ID NOs: 6, 7 or 10.
The system further includes an envelope plasmid comprising a neuron-specific sequence for delivering the shRNA to a neuron, and at least one helper plasmid comprising gag, pol, and rev genes. When the therapeutic vector, the envelope plasmid and the at least one helper plasmid are transfected into a packaging cell line, a neuron-specific lentiviral particle capable of inhibiting PARP1 expression in neurons is produced.
The disclosed content describes neuron-envelope variant comparisons and examples of lentiviral transduction in mouse substantia nigra TH+ neurons, together with proposed MPTP neuroprotection experiments. It also contrasts the approach with AAV and includes extensive construct element descriptions for lentiviral vectors, including LTRs, promoters, cPPT, WPRE, and GFP.
Claims Coverage
The independent claim covers a neuron-targeted lentiviral vector system for Parkinson’s disease that delivers a PARP1-inhibitory shRNA to neurons by neuron-specific envelope-mediated particle production in a packaging cell line. The claim includes four main inventive limitations.
PARP1-inhibitory shRNA with defined sequence identity
The therapeutic vector comprises an encoded shRNA for inhibiting PARP1 expression in neurons, wherein the encoded shRNA comprises at least 80% sequence identity to the entire length of any one of SEQ ID NOs: 6, 7 or 10.
Neuron-specific envelope plasmid for neuronal delivery
An envelope plasmid comprises a neuron-specific sequence for delivering the shRNA to a neuron.
Helper plasmids comprising gag, pol, and rev genes
At least one helper plasmid comprises gag, pol, and rev genes.
Packaging-cell production of neuron-specific lentiviral particles
When the therapeutic vector, the envelope plasmid and the at least one helper plasmid are transfected into a packaging cell line, a neuron-specific lentiviral particle capable of inhibiting PARP1 expression in neurons is produced by the packaging cell line.
Together, the independent claim requires a therapeutic vector encoding a PARP1-inhibitory shRNA constrained by sequence identity, a neuron-specific envelope plasmid for delivery to neurons, helper plasmids carrying gag/pol/rev, and packaging-cell production of neuron-specific lentiviral particles capable of inhibiting PARP1 expression in neurons.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating Parkinson’s disease in a patient in need thereof.
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