Preparatory Mindset

Study this chapter with focus on how genetic principles affect clinical practice.

Core Concepts

• Somatic gene therapy: Correct defect in non-reproductive cells → NOT inherited by offspring


• Germline gene therapy: Correct defect in reproductive cells/embryos → inherited (currently ethically restricted in humans)


• Ex vivo gene therapy: Cells removed from patient, genetically modified, returned to patient


• In vivo gene therapy: Vector (e.g., AAV) delivered directly to patient's cells


• Viral vectors: AAV (non-integrating, safe), Retrovirus (integrating → risk of insertional mutagenesis/cancer)


• CRISPR-Cas9: Targeted gene editing using guide RNA and Cas9 nuclease


• First successful gene therapy: SCID-X1 (adenosine deaminase deficiency) — ex vivo retroviral, cured immune deficiency


• Enzyme replacement therapy: Infuse recombinant enzyme for lysosomal storage diseases (Gaucher, Fabry, Pompe)

High-Yield Points

• Somatic = patient only (NOT inherited); Germline = inheritable (ethically restricted)


• Retroviral vectors → insertional mutagenesis risk (leukemia in SCID-X1 trial)


• CRISPR: precise but off-target effects remain a concern

Topic Summary

Treatment of genetic disease ranges from enzyme replacement to gene therapy. Somatic gene therapy affects only the patient; germline therapy would affect descendants.