METHODS AND COMPOSITIONS FOR DISRUPTING NRF2-KEAP1 PROTEIN INTERACTION BY ADAR MEDIATED RNA EDITING

The present invention relates to methods and compositions for disrupting interaction of an NRF2 protein and a KEAP1 protein. The methods include contacting at least one polynucleotide selected from the group consisting of a polynucleotide encoding the NRF2 protein and a polynucleotide encoding the K...

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Main Authors PUTTA, Mallikarjuna, HERZOG, Kurt, DEVALARAJA, Madhav, LAI, Kevin, CHAPPELL, Todd, KONOPNICKI, Camille, JARPE, Matthew, ERION, Derek, DABNEY, Jesse, SU, Stephen
Format Patent
LanguageEnglish
Published 16.05.2024
Subjects
BEER
BIOCHEMISTRY
CHEMISTRY
COMPOSITIONS THEREOF
CULTURE MEDIA
ENZYMOLOGY
HUMAN NECESSITIES
HYGIENE
MEDICAL OR VETERINARY SCIENCE
METALLURGY
MICROBIOLOGY
MICROORGANISMS OR ENZYMES
MUTATION OR GENETIC ENGINEERING
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS
SPIRITS
VINEGAR
WINE
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Summary:The present invention relates to methods and compositions for disrupting interaction of an NRF2 protein and a KEAP1 protein. The methods include contacting at least one polynucleotide selected from the group consisting of a polynucleotide encoding the NRF2 protein and a polynucleotide encoding the KEAP1 protein with a guide oligonucleotide that effects one or more (e.g., at least two) adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alterations in said at least one polynucleotide, wherein the adenosine to inosine alterations generate a mutant amino acid, thereby disrupting interaction of the NRF2 protein and the KEAP1 protein. The invention also relates to methods of treating a KEAP1-NRF2 pathway related disease in a subject in need thereof, the method comprising contacting, within the subject, at least one polynucleotide selected from the group consisting of a polynucleotide encoding an NRF2 protein and a polynucleotide encoding a KEAP1 protein with a guide oligonucleotide that effects an adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alteration in said at least one polynucleotide, wherein the adenosine to inosine alteration generates a mutant amino acid, thereby disrupting interaction of the NRF2 protein and the KEAP1 protein and treating the disease in the subject; and compositions thereof.
Bibliography:Application Number: AU20220370009