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Allotopic Gene Therapy as a Treatment for Mitochondrial Disease
Author(s) -
Paul Jeremiah,
Palladino Michael J
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.811.9
Subject(s) - mitochondrial encephalomyopathies , mitochondrial dna , biology , mitochondrion , mitochondrial disease , gene , small interfering rna , rna , genetics , computational biology , bioinformatics , microbiology and biotechnology , mitochondrial myopathy
Mitochondrial encephalomyopathies (MEs) result from mutations in mitochondrial genes and have been implicated in the aging process as well as several neurological and neuromuscular diseases. Developing genetic methods to knock‐down (KD) or express (rescue) endogenous mitochondrial genes would enable the development of novel therapies for numerous diseases such as neurodegenerative diseases and mitochondrial disorders, including primary encephalomyopathies such as NARP, MLS, and FBSN. We have shown that RNAs can be targeting to mitochondria including long RNAs capable of coding proteins. Our preliminary data suggest these can be expressed by mitoribosomes but expression appears to be inefficient. We hypothesize that removing 5′UTRs and the targeting elements will dramatically improve the efficiency of mitoribosome translation. One approach we are testing is to engineer mitochondrial‐targeted RNA endonucleases (mtREs); RNA endonuclease, which don't exist in nature, could increase the efficiency of translation in the mitochondria by removing interfering 5′ ribonucleotides. We are testing this hypothesis by engineering clones for studies in HELA cells and transgenic animals for studies in Drosophila. We will examine expression efficiency using confocal microscopy and Western blotting. Support or Funding Information University of Pittsburgh School of Medicine, Summer Undergraduate Research Program (SURP), Molecular Pharmacology Department, Summer 2018 American Society of Pharmacology and Experimental Therapeutics This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .