CRISPR Case Studies: HIV resistant babies, cancer and blindness

In the video - CRISPR Case Studies: Ethical Dilemmas and Revolutionary Applications - I look at the illegal use of CRISPR on babies and its legal use to treat some conditions.

CRISPR has emerged as a powerful genetic engineering tool. However, it does come with the ethical implications.

CRISPR

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene-editing tool that allows scientists to alter DNA sequences within organisms. Using this technology, researchers can add, remove, or modify genetic material, leading to potential cures for genetic diseases, improved agricultural practices, and innovative solutions to environmental issues.

However, using CRISPR, especially in humans, raises significant ethical issues.

The CRISPR Babies

One of the most shocking uses of CRISPR on humans occurred when the genomes of human embryos were edited, leading to the birth of two genetically modified babies. The primary goal was to disable the CCR5 gene to produce babies that were HIV-resistant. That is, remove the receptor that HIV uses to enter human cells.

The CCR5 gene was selected because a naturally occurring mutation in this gene provides resistance to HIV and the Black Death in about 1% of Northern Europeans.

Researchers attempted to mimic this natural 32-base pair deletion using CRISPR, disrupting the CCR5 receptor's function and preventing HIV infection.

Outcomes and Concerns

The resulting edits did not replicate the exact natural mutation. One baby had a 15-base pair deletion in one copy of the gene, while the other had different insertions and deletions across both gene copies.

These unintended mutations raise serious health concerns as studies suggest that individuals with CCR5 mutations may have a 20% lower likelihood of reaching age 76 and could be more susceptible to other infections and diseases.

There is also the risk of off-target edits, where CRISPR inadvertently alters other parts of the genome, potentially leading to unforeseen health issues.

The scientific community widely condemned this work for its ethical breaches, lack of transparency, and disregard for established guidelines. The researchers involved faced legal consequences, including fines and imprisonment.

This case highlights the ethical dilemmas associated with germline editing:

• Consent: The edited changes are heritable, affecting future generations who cannot consent.
• Risk vs. Benefit: The potential health risks may outweigh the intended benefits, especially given existing alternatives to prevent HIV transmission.
• Regulatory Oversight: The need for strict guidelines and oversight in genetic editing research is evident to prevent misuse and ensure ethical compliance.

Promising and Legal Applications of CRISPR

CRISPR has the potential for legitimate and beneficial medical applications. Here are two examples:

1. Cancer Treatment

Treatment of testicular cancer resistant to conventional therapies.

Patient-derived T cells are collected and genetically modified using CRISPR to disrupt three specific genes that regulate T cell targeting. 

A lentivirus is then used to introduce a new targeting mechanism, directing the T cells to recognise and attack proteins unique to the patient's cancer cells.

The modified T cells are then reintroduced into the patient, aiming to boost the immune system's ability to fight cancer effectively.

This represents a personalised and targeted approach to cancer therapy and demonstrates CRISPR's potential to improve immunotherapy treatments.

2. Treating Childhood Blindness

CRISPR is also being used to address Leber Congenital Amaurosis 10 (LCA10), a cause of blindness in children.

The procedure targets the CEP290 gene, where specific mutations disrupt normal retinal development.

The CRISPR components are packaged into adeno-associated viruses (AAVs), and the system precisely removes the mutation in the CEP290 gene, aiming to restore proper protein function and improve vision.