yes or no say in a snetnence In this rationale is there preview of the studies and outcome of the problem like what happend when is not treated The purpose of this research investigation is to gather secondary evidence to discuss how the use of CRISPR technology results in an increase in foetal haemoglobin (HbF) in beta thalassemia.
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a component of the “bacterial” immune system which plays the role of molecular scissors, cutting DNA and re-editing the gene or any transposition factors (Synthego, 2024). Crispr-Cas09 is a revolutionary gene-editing technology that uses an endonuclease to target specific parts of the genome by allowing precise alteration, insertion, or deletion of double-stranded DNA (Redman, King, Watson, King, 2016) and (Your Genome, 2024).
Haemoglobin is a protein inside the red blood cells that facilitates oxygen to the tissues and returns carbon dioxide from the tissues back to the lung to be exhaled (National Cancer Institute, 2011). The differences between adult haemoglobin (Hb) and foetal haemoglobin (HbF) levels in terms of structural differences HbF contains two alpha and gamma subunits, whereas HbA contains two alpha and beta subunits (Kaufman, Khattar, and Lappin, 2023). (Need diagram and a figure legend for this?)
From around 10 to 12 weeks of pregnancy, foetal haemoglobin (HbF) becomes the predominant type of haemoglobin in red blood cells, which continues to be the main haemoglobin type during gestation and starts to decline after birth, with a significant decrease around 6 to 12 months of age (Kaufman, Khattar& Lappin, 2023). Adult haemoglobin A (HbA), the predominant form in mature red blood cells, accounts for approximately 95–98% of total haemoglobin in adults with genetic coding involving four codominant alleles for alpha chains on chromosome 16 and two codominant alleles for beta chains on chromosome 11 (Paul, Firth, 2011).
The inherited blood disorder beta thalassemia, occurs when the normal body is not producing enough beta-globin, leading to symptoms like fatigue, pallor and shortness of breath (Numerous Kidshelath, 2022). The pathophysiology of β-thalassemia involves an imbalance in chain synthesis and an excess of freed α-globin chains accumulating within erythroid cells (Nienhuis and Nathan, 2012).
The chosen claim is: CRISPR technology offers new hope in medicine with a developed research question: How does CRISPR-Cas09 editing of the gene BCL11A affect the clinical nature of thalassemia, as measured by foetal haemoglobin levels and clinical outcomes in patients with β-thalassemia?
BCL11A is a transcriptional repressor that is crucial in brain and hematopoietic system development, as well as foetal-to-adult haemoglobin switching (Yin, Xie, Ye, Wang and Che, 2019). In thalassemia, BCL11A inhibits y-globin expression and foetal haemoglobin throughout the body (Frangoul, Altshuler, Cappellini, Chen, Domm, Eustace, Foell, de la Fuente, Heandgretinger, Kattamis, Kernytsky, Lekstrom-Himes, Locatelli, Mapara, Montalembert, Rondelli, and Sharama, 2020). Theoretically, CRISPR- Cas09 could treat thalassemia by targeting the BCL11A gene, which plays a crucial role in regulating the levels of haemoglobin F (Goodman, 2024).
The mortality rate of thalassemia globally in 2021 was 0.15 per 100,000 persons (95% UI 0.11–0.20). (Tuo, Li, Li, Ma, Yang, Wu, Jin and He, 2024). The use of CRISPR-Cas09 could therefore decrease mortality by correcting the underlying genetic mutations that cause thalassemia, potentially leading to more effective and long-lasting treatments.
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