Browsing by Subject "RNA splicing"

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    Changing the landscape of non-small cell lung cancer disparities.
    (Journal of cancer biology, 2021-01) Odera, Joab O; Abo, Muthana Al; Patierno, Steven R; Clarke, Jeffrey M; Freedman, Jennifer A
    In the United States, lung and bronchus cancers are the second most common types of cancer and are responsible for the largest number of deaths from cancer, with African Americans suffering disproportionately from lung and bronchus cancers. This disparity likely results from a complex interplay among social, psycho-social, lifestyle, environmental, health system, and biological determinants of health. Toward improving outcomes for lung cancer patients of all races and ethnicities and mitigating lung cancer disparities, in this commentary, we bring forward biological factors that contribute to lung cancer disparities, efforts to identify, functionally characterize, and modulate novel ancestry-related RNA splicing-related targets in lung cancer for precision intervention, and translational and clinical research needs to improve outcomes for lung cancer patients of all races and ethnicities and mitigate lung cancer disparities.
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    Using Nucleic Acids to Repair β-Globin Gene Mutations
    (2007-05-02T17:38:03Z) Kierlin-Duncan, Monique Natasha
    Nucleic acids are an emerging class of therapeutics with the capacity to repair both DNA and RNA mutations in clinically relevant targets. We have used two approaches, mobile group II introns and Spliceosome Mediated RNA Trans-splicing (SMaRT), to correct β-globin mutations at the DNA and RNA levels respectively. We show that the group II intron inserts site-specifically into its DNA target, even when similar targets are available. Experiments transitioning this therapeutic into mammalian cell systems are then described. We also illustrate how SMaRT RNA repair can be used to correct β-globin mutations involved in sickle cell disease and some forms of β- thalassemia. We uncovered diverse repair efficiencies when targeting sickle cell versus β- thalassemia transcripts in mammalian cells. Possible reasons for this and how it might direct target choice for the SMaRT therapeutic approach are both discussed. The therapeutic molecule in SMaRT, a Pre-Trans-splicing Molecule or PTM, is also delivered via lentivirus to erythrocyte precursors cultured from the peripheral blood of sickle cell patients. Preliminary results from these experiments are discussed.