Modulation of acmsd protein expression
AssigneesDignity Health, Board of Trustees of Michigan State University, Van Andel Research Institute
InventorsFredric Manfredsson, Lena Brundin
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Abstract
Compositions for increasing the expression of ACMSD in a target cell and methods of using the compositions to provide a general protective effect in a cell or tissue in a subject, or protect a subject from or treating a disease condition associated with inflammation, oxidative stress, protein aggregation, energy failure, toxic exposure such as exposure to pollutants, or any combination thereof.
Claims85
An expression construct for expressing an aminocarboxymuconate semialdehyde decarboxylase (ACMSD) protein in a target cell, the expression construct comprising:
- a. a promoter operably linked to a nucleic acid sequence encoding a programmable nucleic acid modification system targeted to a nucleic acid sequence in a nucleotide sequence encoding the ACMSD protein;
- or
- b. a promoter operably linked to a nucleotide sequence encoding the ACMSD protein.
The expression construct of any one of the preceding claims, wherein a cell comprising the expression construct comprises increased the expression of the ACMSD protein to levels higher than levels normally found in cells.
The expression construct of any one of the preceding claims, wherein a cell comprising the expression construct comprises increased the expression of the ACMSD protein to levels higher than levels in cells having defective levels of ACMSD expression.
The expression construct of any one of the preceding claims, wherein the amino acid sequence of the ACMSD protein comprises about 75% or more, 85% or more, 95% or more, or 100% sequence identity with SEQ ID NO:
- 6.
The expression construct of any one of the preceding claims, wherein the target cell is liver, kidney, placenta, brain, cancer cells or tumors, cells of the immune system, or any combination thereof.
The expression construct of any one of the preceding claims, wherein the target cell is a cell of the central nervous system.
The expression construct of any one of the preceding claims, wherein the target cell is a neural cell.
The expression construct of any one of the preceding claims, wherein the target cell is a cell of glial lineage.
The expression construct of any one of the preceding claims, wherein the target cell is an astrocyte.
The expression construct of any one of the preceding claims, wherein the target cell is a glial cell.
The expression construct of any one of the preceding claims, wherein the target cell is in a subject suffering from inflammation, or a disorder associated with inflammation.
The expression construct of any one of the preceding claims, wherein the target cell is in a subject suffering from a condition associated with inflammation, oxidative stress, protein aggregation, energy failure, toxic exposure such as exposure to pollutants, genetic factors, environmental conditions, immune system activity, or any combination thereof.
The expression construct of any one of the preceding claims, wherein the target cell is in a subject suffering from a neurological disorder or a psychiatric disorder.
The expression construct of any one of the preceding claims, wherein the promoter is a tissue or cell-specific promoter control sequence.
The expression construct of any one of the preceding claims, wherein the engineered vector-mediated system comprises a nucleic acid expression construct comprising a promoter operably linked to a nucleotide sequence encoding the ACMSD protein.
The expression construct of any of the preceding claims, further comprising a nucleic acid delivery vector comprising the nucleic acid expression construct for delivering the nucleic acid expression construct to the target cell.
The method of any one of the preceding claims, wherein the target cell is a cell of the central nervous system.
The method of any one of the preceding claims, wherein increasing the expression of ACMSD in cells of the nervous system provides a neurotrophic effect.
The method of any one of the preceding claims, wherein the disease condition is associated with quinolinic acid.
The method of any one of the preceding claims, wherein the disease condition is associated with inflammation.
The method of any one of the preceding claims, wherein the disease condition is associated with neuroinflammation.
The method of any one of the preceding claims, wherein the disease condition is a neurological or psychiatric disorder.
The method of any one of the preceding claims, wherein providing a general protective effect comprises providing protection from pathological conditions associated with inflammation, oxidative stress, protein aggregation, energy failure, toxic exposure such as exposure to pollutants, genetic factors, environmental conditions, immune system activity, or any combination thereof.
The method of any one of the preceding claims, wherein providing a general protective effect comprises providing protection from disease conditions associated with quinolinic acid.
The method of any one of the preceding claims, wherein providing a general protective effect comprises providing protection from disease conditions associated with inflammation.
The method of any one of the preceding claims, wherein the general protective effect is a neurotrophic effect.
The method of any one of the preceding claims, wherein providing a general protective effect comprises providing protection from disease conditions associated with neuroinflammation.
The method of any one of the preceding claims, wherein providing a general protective effect comprises providing protection from Parkinson's disease, Alzheimer's disease, ALS, Huntington's disease, brain ischemia, CNS infections and autoimmune disorders, mood disorders, schizophrenia, or any combination thereof.
Dependencies are inferred from the claim text.