UNIT 5: Gene Therapy and Human Genetic Engineering

Exam Focus: The distinction between the two main types of gene therapy (**Somatic vs. Germline**) and the major **ethical concerns** (e.g., eugenics, safety) are paramount. Also, know the difference between the **In-vivo** and **Ex-vivo** approach for delivery.

Gene Therapy
Human Genetic Engineering
- Problems and Ethics

1. Gene Therapy

Definition

Gene therapy is a technique that involves the insertion of a normal or therapeutic gene into a patient's cells instead of a defective gene to treat a disease, especially genetic disorders.

Types (In-vivo and Ex-vivo)

Gene therapy is classified based on where the genetic modification takes place:

Type	Mechanism	Example
In-vivo (in the body)	Therapeutic gene (in a vector, e.g., AAV) is injected directly into the patient's body to target cells in situ.	Treatment of retinal diseases (direct injection into the eye).
Ex-vivo (out of the body)	Patient cells are isolated, modified/corrected in vitro (e.g., by adding the normal gene), and then re-introduced back into the patient.	Correction of immune cells for SCID (Severe Combined Immunodeficiency).

Application

Gene therapy is primarily aimed at curing or alleviating genetic and acquired diseases:

**Genetic Diseases:** SCID (Bubble Boy disease), Haemophilia, Cystic Fibrosis.
**Acquired Diseases:** Cancer (using CAR T-cell therapy), HIV infection.

Challenges

**Vector Safety:** Potential for the viral vector (used for delivery) to cause an immune reaction or disease.
**Target Specificity:** Ensuring the therapeutic gene reaches and integrates only into the correct cell type.
**Gene Expression Control:** Difficulty in controlling the level and duration of the therapeutic gene's expression.
**Cost:** High cost of development and treatment.

Ethical Issues

The core ethical debates revolve around the boundary between therapy and enhancement, and the heritability of the change.

**Somatic vs. Germline Therapy:**
- **Somatic Gene Therapy:** Involves modifying somatic cells (non-reproductive) and is generally ethically acceptable, as the changes are **not inherited**.
- **Germline Gene Therapy:** Involves modifying reproductive cells (sperm/egg or early embryo). These changes **are inherited** by future generations. It is currently banned in most countries due to ethical and safety concerns (unforeseen long-term effects on the human gene pool).
**Enhancement vs. Therapy:** The concern that gene therapy might be used for human enhancement (e.g., improving intelligence or athleticism) rather than just treating disease.

2. Human Genetic Engineering

Problems and Ethics

Human genetic engineering refers to modifying the genes of human cells to correct defects or confer new traits.

**Safety and Irreversibility:** The primary technical problem is the risk associated with non-specific gene integration and the impossibility of reversing germline changes.
**Eugenics Concerns:** The fear that genetic engineering will be used to create "designer babies" or lead to social discrimination based on genetic makeup, promoting a new form of eugenics.
**Informed Consent:** Obtaining valid and ethical informed consent, especially when dealing with embryos or germline changes affecting future, non-consenting generations.