Cystic Fibrosis:
Gene Therapy
Ellie Johnson, Claire Strauel, Sam Bennett, Ashley Nelson
Background
- Disease that damages lungs and other organs
- Caused by defective CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene
- Test through sweat test and blood test
Background
Signs/Symptoms
Signs/Symptoms
- Persistant cough (with phlegm)
- Wheezing/shortness of breath
- Poor growth and weight gain
- Frequent greasy stool and difficult bowel movement
- Enlarged fingertips and toes
What is Gene
Therapy?
- Modifies how a gene is expressed
- Treats diseases using replacement, inactivation, and introduction
- Two types: In Vivo and Ex Vivo
Gene Therapy
Overview
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy
Gene Therapies Used In CF
Gene Therapy in CF
- integrating gene therapy
- correct CFTR gene integrated into the genome.
- non-integrating gene therapy
- correct CFTR gene is placed in the cell, but does not integrate into the genome.
- RNA therapy
- RNA replaces or repairs the mutated mRNA.
Therapeutic Gene Editing in CF: CRISPR/Cas9
- RNA/protein complex that corrects the genetic mutations themselves.
- Three main components:
- "Guide" RNA
- "scissors" Cas9 nuclease
- template strand
- Allows for regulation at transcriptional level.
- Still being tested, could be years before this is used to treat humans with CF.
Helpful Video
https://www.youtube.com/watch?v=Sp774i6tdzE&t=9s
Side Effects
Side Effects of Gene Therapy directly related to CF
- Weight gain
- Neurological issues (dizziness)
- Pulmonary exacerbations
General Side Effects of Gene Therapy
- Increased Risk of Cancer
- Immune reaction
- May target wrong cell
- Infection
https://play.kahoot.it/v2/?quizId=370e4437-9c24-41f4-97a9-a6e8afd98e4e
Kahoot!
Sources
- Carlon, Marianne, Vidović, Dragana, & Birket, Susan. (2017). Roadmap for an early gene therapy for cystic fibrosis airway disease. Prenatal Diagnosis, 37(12), 1181–1190.
- “Gene Editing for Cystic Fibrosis: Cystic Fibrosis Foundation.” Gene Editing for Cystic Fibrosis | Cystic Fibrosis Foundation.
- Center for Biologics Evaluation and Research. (2018). What is gene therapy? U.S. Food and Drug Administration. Retrieved November 16, 2021, from https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy.
- Ziying Yan, Paul B McCray Jr, John F Engelhardt, Advances in gene therapy for cystic fibrosis
lung disease, Human Molecular Genetics, Volume 28, Issue R1, October 2019, Pages
R88–R94, https://doi.org/10.1093/hmg/ddz139
- Skilton M, Krishan A, Patel S, Sinha IP, Southern KW. Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis. Cochrane Database of Systematic Reviews 2019, Issue 1. Art. No.: CD009841. DOI: 10.1002/14651858.CD009841.pub3.
- Mayo Foundation for Medical Education and Research. (2017, December 29). Gene therapy. Mayo Clinic. Retrieved November 16, 2021, from https://www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-20384619.
Sources