Gene therapy is a rapidly advancing biomedical field aimed at correcting genetic defects. Depending on the target cell population, these therapeutic interventions are categorized as either somatic or germ-line.
CRISPR-Cas9 genome editing can be applied in two clinical pathways: Group A involves editing mature T-lymphocytes to treat leukemia, while Group B involves editing pre-implantation embryos. State which group's genetic modifications can be inherited by future offspring, and explain why.
Compare somatic and germ-line gene therapy with respect to:
In clinical trials for X-linked Severe Combined Immunodeficiency (SCID-X1), researchers used a retroviral vector to integrate a functional copy of the missing IL2RG gene into patients' hematopoietic stem cells. However, some patients subsequently developed T-cell leukemia because the viral genome integrated near the LMO2 proto-oncogene.
Explain how the insertion of a therapeutic gene sequence can alter the expression and function of a neighboring host gene.
Adenosine Deaminase (ADA) deficiency is an autosomal recessive metabolic disorder that can be treated by introducing a normal, functional copy of the ADA gene (gene addition therapy).
In contrast, familial Amyotrophic Lateral Sclerosis (fALS) can be caused by a dominant mutation in the SOD1 gene, which codes for a misfolded, toxic enzyme that aggregates and kills motor neurons.
Suggest why standard gene addition therapy is unlikely to be an effective treatment for this form of fALS.
