Sample Notes: Genetic Technology Applied To Medicine

A2 Biology – Genetic Technology Applied to Medicine

1. Recombinant Human Proteins for Disease Treatment

Definition & Overview

• Recombinant DNA technology involves inserting human genes into bacteria or other host organisms to produce human proteins.
• These recombinant proteins are purified and used medically, especially when natural sources are unavailable, insufficient, or risky.

Advantages of Recombinant Human Proteins

• Purity & Consistency: No risk of contamination with animal viruses or prions.
• Supply Reliability: Unlimited production; not dependent on human donors or cadavers.
• Fewer Immune Reactions: Human-identical proteins lower the chance of immune response.
• Ethical Acceptability: Avoids use of animal tissues or products.

Examples

1. Insulin (for Diabetes Mellitus)

• Old method: Porcine/bovine insulin—often caused allergic reactions.
• Recombinant method: Human insulin gene inserted into E. coli → Insulin harvested and purified.
• Benefits:
  • Structurally identical to endogenous insulin.
  • Faster-acting forms and long-acting analogs now possible.
  • Improved blood glucose control and patient quality of life.

2. Factor VIII (for Hemophilia A)

• Function: Clotting factor; its deficiency causes prolonged bleeding.
• Traditional source: Donor plasma (risk of HIV/hepatitis).
• Recombinant source: Genetically modified hamster ovary cells or other mammalian cell cultures.
• Advantages:
  • Safe from blood-borne infections.
  • Stable supply for lifelong treatment.
  • Better patient outcomes with prophylactic use.

3. Adenosine Deaminase (for SCID)

• Function: Enzyme that breaks down deoxyadenosine, toxic to lymphocytes.
• ADA-SCID: Autosomal recessive disorder → severe immune deficiency.
• Recombinant therapy: Synthetic ADA administered to boost immune function.
• Limitations:
  • Temporary effects; repeated injections needed.
  • Gene therapy is now considered a more permanent solution.

2. Genetic Screening

Definition

• Testing an individual’s DNA to detect presence or risk of genetic disorders.
• Can be done prenatally, postnatally, or for adults with family history.

Advantages

• Early diagnosis and preventive action.
• Informs reproductive decisions.
• Personalized treatment and risk management.
• May reduce long-term healthcare costs.

Key Applications

1. Breast Cancer (BRCA1 & BRCA2)

• BRCA1/2 mutations: Strongly linked to hereditary breast and ovarian cancers.
• Inheritance: Autosomal dominant.
• Implications of screening:
  • Increased surveillance (mammography, MRI).
  • Preventive surgeries (e.g. mastectomy).
  • Lifestyle adjustments and prophylactic treatments.

2. Huntington’s Disease

• Nature: Autosomal dominant; CAG repeat expansion in HTT gene.
• Features: Neurodegeneration, personality changes, late onset (30s-50s).
• Screening use:
  • Predictive testing for at-risk individuals.
  • Psychological counseling essential due to emotional burden.
  • No cure yet, but early preparation helps in planning.

3. Cystic Fibrosis

• Gene affected: CFTR (autosomal recessive).
• Effects: Thick mucus → respiratory, digestive issues.
• Screening:
  • Newborn screening programs in many countries.
  • Carrier testing in couples.
  • Early treatment → reduced lung infections, better nutrition.

3. Gene Therapy

Definition

• Introduction, removal, or alteration of genes within a patient’s cells to treat disease.
• Delivered via viral vectors (e.g. retroviruses, adenoviruses) or non-viral methods (e.g. liposomes).

Types

• Somatic gene therapy: Affects only body (non-germline) cells; changes not inheritable.
• Germline gene therapy: Affects sperm/egg cells; inheritable (currently banned in humans due to ethical concerns).

Examples of Gene Therapy in Medicine

1. SCID (Severe Combined Immunodeficiency)

• Caused by mutations in genes like ADA or IL2RG.
• ADA-SCID patients cannot mount immune responses.
• Gene therapy:
  • Ex vivo approach: Patient’s stem cells modified to express functional ADA.
  • Cells reintroduced into body to restore immune function.
  • Successful trials: Long-term immune reconstitution in children.
  • Complication: Risk of leukemia in earlier retroviral therapies.

2. Inherited Eye Diseases (e.g., Leber’s Congenital Amaurosis)

• Caused by RPE65 gene mutations.
• Progressive blindness starting in infancy.
• Treatment:
  • AAV (adeno-associated virus) carrying functional gene injected into retina.
  • Improves light sensitivity and vision.
  • First FDA-approved gene therapy for inherited disease.

4. Social and Ethical Considerations

Concerns in Genetic Screening

• Psychological impact: Anxiety, depression from knowing genetic risk.
• Discrimination: In employment or insurance based on genetic data.
• Informed consent: Patients must understand what the results mean.
• Privacy: Genetic information must be confidential and securely stored.

Concerns in Gene Therapy

• Unintended consequences: Insertional mutagenesis, immune responses.
• Access and equity: Expensive therapies may only benefit the rich.
• Eugenics fears: Potential future misuse to select for desired traits.
• Germline modification: Ethical debate over altering future generations.
• Cultural/religious objections: Some groups may reject DNA manipulation.

Balancing Benefits and Risks

• Proper regulation, public education, and ethical frameworks are crucial.
• Benefit to patients with previously untreatable conditions is immense.
• Ongoing research into safer and more efficient delivery systems is essential.

Summary Table: Comparison of Applications

Key Terms