Genetically modified probiotic for the treatment of phenylketonuria (PKU) disease
A GMP adapted to provide the PAL gene for the treatment of PKU when administered orally. The GMP of the present invention may include a probiotic, a PAL gene to be expressed using the probiotic, wherein the PAL gene is functionally attached to a promoter and a ribosome binding site, and may be codon-optimized for expression in a certain host organism. A method of treating the metabolic disease of PKU by oral administration and ingestion of a GMP is also provided.
1. A composition for treating phenylketonuria, comprising:
a probiotic bacterium from the Lactobacillus genera selected from the group consisting of Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus casei, Lactobacillus plantarum , and Lactobacillus reuteri , wherein the probiotic bacterium is genetically modified to express an exogenous nucleotide sequence encoding a functional phenylalanine ammonia-lyase (PAL) enzyme protein, and wherein the nucleotide sequence encoding the phenylalanine ammonia-lyase (PAL) comprises SEQ ID NO:15.
2. The composition of claim 1 , wherein the nucleotide sequence encoding the phenylalanine ammonia-lyase (PAL) is integrated into the chromosome of the probiotic bacterium.
3. The composition of claim 1 , wherein the probiotic bacterium carries a recombinant plasmid vector comprising the nucleotide sequence encoding the phenylalanine ammonia-lyase (PAL), and wherein the recombinant plasmid vector comprises a nucleotide sequence comprising SEQ ID NO: 13 or SEQ ID NO:14.
4. The composition of claim 1 , wherein the probiotic bacterium is Lactobacillus reuteri.
5. The composition of claim 1 , wherein the probiotic bacterium is Lactobacillus acidophilus.
6. A method for administering a composition for treating phenylketonuria, comprising the step of:
administering a therapeutically effective amount of the composition of claim 1 to a patient in need thereof, wherein said administration is oral.
7. A composition for treating phenylketonuria, comprising:
a probiotic bacterium, wherein the probiotic bacterium is Lactobacillus acidophilus , wherein the probiotic bacterium is genetically modified to integrate an exogenous nucleotide sequence encoding a functional phenylalanine ammonia-lyase (PAL) enzyme protein into the chromosome of the probiotic bacterium, wherein the probiotic bacterium expresses the nucleotide sequence encoding the phenylalanine ammonia-lyase (PAL), and wherein the nucleotide sequence encoding the phenylalanine ammonia-lyase (PAL) comprises SEQ ID NO: 15.