Xiao Wang
University of Pennsylvania, PA·Genetics
Phenylketonuria, or PKU, is an inherited disease in which a liver enzyme that breaks down the amino acid phenylalanine is broken. Phenylalanine then builds up to levels that harm the developing brain.
- Fields
Genetics
Medicine & Clinical Research
Pharmacology
- Topics
phenylketonuria
phenylalanine hydroxylase
base editing
- Grants
- 1 known grant, through May 2029
What they work on
- Test whether adenine base editors, which chemically rewrite a single DNA base without cutting both strands, can correct the PAH R408W variant in cultured human liver cells and restore phenylalanine hydroxylase activity.
- Test whether prime editing, which writes a short programmed DNA sequence at a chosen site, can correct the same PAH R408W variant, and compare its efficiency against base editing.
- Deliver the leading editors in vivo to humanized mice carrying the human PAH R408W variant and measure editing efficiency in the liver along with blood phenylalanine levels.
- Assess safety by quantifying off-target DNA edits and unintended changes in liver tissue, to determine which editing system is best suited for translation.
More about the research
Current options are a lifelong strict low-phenylalanine diet, a pill (sapropterin) that helps the enzyme work, or an injected enzyme replacement (pegvaliase), but many patients cannot stick to the diet or do not respond to the drugs, and go on to have cognitive and neuropsychiatric problems. A one-time treatment that fixes the underlying DNA change would address that gap.
Why it matters
A single-dose DNA correction could spare people with PKU from lifelong dietary restriction and repeated injections, and would offer an option to patients with the common R408W variant who do not respond to sapropterin. If the approach works, it may extend to other correctable PAH mutations and to other inherited diseases caused by mutations in genes expressed in the liver.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
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The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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