Back to results
US 2023/0136245 A1Published application
Gene therapy for neurodegenerative disorders using polynucleotide silencing and replacement
AssigneeParos Bio, Inc.
InventorsKimberley S. Gannon, Neil R. Hackett, Martin Goulet
Life of this patent
Estimating the term…
Abstract
The disclosure relates to nucleic acid expression cassettes and vectors for the treatment of neurodegenerative disorders. Methods of treating neurodegenerative disorders such as Alzheimer's disease, frontotemporal dementia, frontotemporal lobar degeneration, Pick's disease, Lewy body dementia, memory loss, cognitive impairment, and mild cognitive impairment are also provided.
Claims29
An expression cassette comprising:
- a. a first polynucleotide encoding one or more short hairpin RNAs or (shRNAs) or micro RNAs (miRNAs), each of which independently targets a coding region or a non-coding region of an endogenous messenger RNA (mRNA) derived from each of a human wild-type and a mutant presenilin 1 (PSEN1) or from each of a human wild-type and a mutant presenilin 2 (PSEN2), wherein each of the one or more shRNAs or miRNAs is operably linked to one or more first promoters;
- and
- b. a second polynucleotide encoding a wild-type presenilin 1 (PSEN1) or presenilin 2 (PSEN2) amino acid sequence, wherein the second polynucleotide is not targeted by any of the shRNAs or miRNAs encoded by the first polynucleotide;
- and wherein the second polynucleotide is operably linked to a second promoter.
1 more element
A set of vectors comprising:
- a. a first vector comprising an expression cassette comprising a first polynucleotide encoding one or more shRNAs or miRNAs targeting either a coding region or a non-coding region of a mRNA translated from each of a human wild-type and a mutant presenilin 1 (PSEN1), or from each of a human wild-type and a mutant presenilin 2 (PSEN2), wherein each of the one or more shRNAs or miRNAs is operably linked to one or more first promoters;
- and
- b. a second vector comprising a second polynucleotide encoding a wild-type presenilin 1 (PSEN1) amino acid sequence or a wild-type presenilin 2 (PSEN2) amino acid sequence, wherein the second polynucleotide is not targeted by any of the shRNAs or miRNAs encoded by the first vector;
- and wherein the second polynucleotide is operably linked to a second promoter.
1 more element
A kit comprising:
- a. one or more antisense oligonucleotides, wherein each antisense oligonucleotide independently targets either a coding region or a non-coding region of an mRNA translated from each of a human wild-type and mutant presenilin 1 (PSEN1), each of a human wild-type or mutant presenilin 2 (PSEN2);
- and
- b. a vector comprising a polynucleotide encoding a wild-type presenilin 1 (PSEN1) amino acid sequence or a wild-type presenilin 2 (PSEN2) amino acid sequence, wherein the second polynucleotide is not targeted by any of the one or more antisense oligonucleotides;
- and wherein the polynucleotide is operably linked to a promoter in the vector.
1 more element
An isolated nucleic acid sequence comprising SEQ ID NO:
- 41.
Dependencies are inferred from the claim text.