Compositions and methods for the management and treatment of phenylketonuria
AssigneesThe Trustees of the University of Pennsylvania, The Children's Hospital of Philadelphia
InventorsKiran Musunuru, Xiao Wang, Dominique Lynnette Brooks, Rebecca Ahrens-Nicklas
Life of this patent
Estimating the term…
Abstract
Compositions and methods for effecting base editing to correct mutations in the phenylalanine hydroxylase gene, thereby curing phenylketonuria, are disclosed.
Claims20
A method for editing a phenylalanine hydroxylase (PAH) encoding polynucleotide comprising a c.1222C>T (p.Arg408Trp) mutation, the method comprising contacting the PAH polynucleotide with a base editor in complex with at least one guide polynucleotide, wherein the base editor comprises a polynucleotide programmable DNA binding domain and an adenosine deaminase domain, and wherein one or more of said guide polynucleotides target said base editor to effect an A·T to G·C alteration of the mutation.
An adenosine base editor/guide polynucleotide set which corrects a mutation causing PKU comprising:
- (i) a modified SpCas9 or SaCas9;
- (ii) an adenosine deaminase or functional fragment thereof;
- and
- iii) a guide polynucleotide that targets the base editor to effect an A·T to G·C alteration of a c.1222C>T (p.Arg408Trp) mutation associated with PKU.
Dependencies are inferred from the claim text.