Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU

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dc.creatorDurrer, Katherine E.
dc.creatorAllen, Michael S.
dc.creatorHunt von Herbing, Ione
dc.creator.orcid0000-0003-2293-8078 (Allen, Michael S.)
dc.date.accessioned2022-08-24T21:30:30Z
dc.date.available2022-08-24T21:30:30Z
dc.date.issued2017-05-17
dc.description.abstractPhenylketonuria (PKU) is a genetic disease characterized by the inability to convert dietary phenylalanine to tyrosine by phenylalanine hydroxylase. Given the importance of gut microbes in digestion, a genetically engineered microbe could potentially degrade some ingested phenylalanine from the diet prior to absorption. To test this, a phenylalanine lyase gene from Anabaena variabilis (AvPAL) was codon-optimized and cloned into a shuttle vector for expression in Lactobacillus reuteri 100-23C (pHENOMMenal). Functional expression of AvPAL was determined in vitro, and subsequently tested in vivo in homozygous PAHenu2 (PKU model) mice. Initial trials of two PAHenu2 homozygous (PKU) mice defined conditions for freeze-drying and delivery of bacteria. Animals showed reduced blood phe within three to four days of treatment with pHENOMMenal probiotic, and blood phe concentrations remained significantly reduced (P < 0.0005) compared to untreated controls during the course of experiments. Although pHENOMMenal probiotic could be cultured from fecal samples at four months post treatment, it could no longer be cultivated from feces at eight months post treatment, indicating eventual loss of the microbe from the gut. Preliminary screens during experimentation found no immune response to AvPAL. Collectively these studies provide data for the use of a genetically engineered probiotic as a potential treatment for PKU.
dc.description.sponsorshipThis work was supported by National PKU Alliance, http://npkua.org/Research/Scientific-Grant-Requests, received scientific seed money grant for 2 years, 2012-2014; National Society for PKU (England), http://www.nspku.org/ donated$10,000.00 as supplement funds, not an official grant. The funders had no role in study design, data collection/analysis, decision to publish, or preparation of the manuscript.
dc.identifier.citationDurrer, K. E., Allen, M. S., & Hunt von Herbing, I. (2017). Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU. PloS one, 12(5), e0176286. https://doi.org/10.1371/journal.pone.0176286
dc.identifier.issn1932-6203
dc.identifier.issue5
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31634
dc.identifier.volume12
dc.publisherPLOS
dc.relation.urihttps://doi.org/10.1371/journal.pone.0176286
dc.rights.holder© 2017 Durrer et al.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePLoS One
dc.subject.meshAnimals
dc.subject.meshBacteria / classification
dc.subject.meshBacteria / genetics
dc.subject.meshCluster Analysis
dc.subject.meshDNA, Bacterial / chemistry
dc.subject.meshDNA, Bacterial / genetics
dc.subject.meshDNA, Ribosomal / chemistry
dc.subject.meshDNA, Ribosomal / genetics
dc.subject.meshEnvironmental Exposure
dc.subject.meshIxodes / microbiology
dc.subject.meshMicrobiota / radiation effects
dc.subject.meshPhylogeny
dc.subject.meshRNA, Ribosomal, 16S / genetics
dc.subject.meshSequence Analysis, DNA
dc.subject.meshTemperature
dc.subject.meshUnited States
dc.titleGenetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU
dc.typeArticle
dc.type.materialtext

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