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Date of Award

Spring 2025

Degree Name

Master of Medical Science (Physician Assistant)

Department

Physician Assistant; College of Health Sciences

First Advisor

Jessica Hammerman, MMS, PA-C

Abstract

Sickle cell disease is a life-threatening, inherited blood disorder affecting millions globally. It results from a single point mutation in the β-globin gene, leading to abnormal hemoglobin S and distorted red blood cells that cause vaso-occlusion, anemia, pain crises, and organ damage. While traditional therapies such as pain control, hydroxyurea, and blood transfusions provide symptomatic relief, they are not curative and come with significant limitations.

CRISPR-Cas9, a revolutionary gene-editing technology, offers a novel therapeutic approach. Utilizing a guide RNA and Cas9 endonuclease, the system precisely targets and edits DNA, either repairing the sickle mutation or enhancing fetal hemoglobin production. In December 2023, the FDA approved the first CRISPR-based therapy for sickle cell disease, known as, Casvegy, marking a significant milestone in genomic medicine.

Despite its promise, CRISPR-Cas9 presents challenges including high cost, accessibility barriers, potential off-target genetic effects, and ethical concerns regarding germ-line transmission. However, early clinical results are encouraging, suggesting significant symptom relief and improved quality of life.

This poster explores the mechanism, clinical application, and future implications of CRISPR-Cas9 in sickle cell disease. It highlights the need for ongoing research, ethical deliberation, and equitable access as gene editing becomes the cornerstone of modern medicine.

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CRISPR-Cas9 - The Future of Sickle Cell Disease Management

Sickle cell disease is a life-threatening, inherited blood disorder affecting millions globally. It results from a single point mutation in the β-globin gene, leading to abnormal hemoglobin S and distorted red blood cells that cause vaso-occlusion, anemia, pain crises, and organ damage. While traditional therapies such as pain control, hydroxyurea, and blood transfusions provide symptomatic relief, they are not curative and come with significant limitations.

CRISPR-Cas9, a revolutionary gene-editing technology, offers a novel therapeutic approach. Utilizing a guide RNA and Cas9 endonuclease, the system precisely targets and edits DNA, either repairing the sickle mutation or enhancing fetal hemoglobin production. In December 2023, the FDA approved the first CRISPR-based therapy for sickle cell disease, known as, Casvegy, marking a significant milestone in genomic medicine.

Despite its promise, CRISPR-Cas9 presents challenges including high cost, accessibility barriers, potential off-target genetic effects, and ethical concerns regarding germ-line transmission. However, early clinical results are encouraging, suggesting significant symptom relief and improved quality of life.

This poster explores the mechanism, clinical application, and future implications of CRISPR-Cas9 in sickle cell disease. It highlights the need for ongoing research, ethical deliberation, and equitable access as gene editing becomes the cornerstone of modern medicine.