Limitless Potential

This versatile tool gives us the power to control gene expression in plants, animals, and even humans. With the ability to eradicate undesirable genes or undesirable mutations in genes, the CRISPR-Cas9 technology has the potential to revolutionize patient treatment. There are about 10,000 diseases caused by modifications in a single gene, however the application is not limited to those. The following are just a few of the diseases that the CRISPR-Cas9 technology could potentially cure.

• cancer; e.g. 30% of all cancer is driven by activating mutations of RAS gene
• blood disorders; e.g. beta-thalassemia caused by inherited mutations in HBB gene
• infectious disease; e.g. inactivating mutations to HIV virus

 In addition, CRISPR-Cas9 technology has been implemented by another revolutionary treatment method called Chimeric Antigen Receptor (CAR) T cell therapy. CAR-T and CRISPR are used to harnesses the power of the human immune system in cancer treatment.

With Great Power Comes Great Responsibility

In this early stage of development, CRISPR-based therapeutics faced some challenges including its delivery, safety, and pharmacology. Introducing a complex set of components into an individual organ system and delivering those components to the right organs is complicated. The off-target effect where CRISPR activity is observed in unintended parts of the genome poses risks to safety. After the first human trials were initiated, two reports in Nature Medicine emerged associating the technology with a cancer risk. Both reports focused on the classic tumor suppressor gene (p53), whose activation induces apoptosis, cell cycle arrest, or senescence in response to distinct stimuli, including DNA damage or aberrant oncogene activation.  Haapaniemi et al. showed that cutting the genome with CRISPR-Cas9 induced the activation of p53. Ihry et al. emphasized the necessity to ensure functional p53 before and after gene edited cells. These findings suggest “if CRISPR worked, it was because p53 didn’t” raising concerns of cancer risk in patients.

Throughout its development, the challenges will shift to other areas such as clinical benefit to the patients and commercialization. Determining a reasonable pricing to balance the curative potential of these treatments will be an additional key point to address.

There are also ethical concerns that arise in genome editing to alter human embryos. A Chinese scientist claimed to have helped make the world’s first genome-edited babies in November 2018 by disabling a gene called CCR5 so the twins would develop resistance to potential infection with HIV. This news stimulated an outcry from the global scientific community. The World Health Organization announced the establishment of an international committee to devise guidelines for human gene editing. The first meeting will be held in March 2019.

It’s Only the Beginning

Considering that gene editing is in its infancy, it is difficult to precisely predict its growth prospects.  It has been one of the most exciting discoveries of the last decade with its potential to treat human disease. Despite a few hurdles, it is a fast-moving field, and there has already been progress to overcome off-target effects by selecting RNA guides carefully. A deeper understanding in human genome and genetic driver of disease or conditions will likely lead to broader applications for CRISPR-Cas9 technology. In “Human Nature”, a scientific documentary, key scientists involved in gene-editing technology assert that “the biggest tech revolution of the 21st century isn’t digital, it’s biological”. Indeed, this groundbreaking and controversial the gene-editing tool has the potential to fix disease, eradicate cancer, and drive a revolution in the medical community.

Sources:

“CRISPR/Cas9 in Genome Editing and Beyond”, Wang et al. Annuals Review of Biochemistry 2016

“Identification of Causal Genetic Drivers of Human Disease through Systems-Level Analysis of Regulatory Networks” Chen et al. Cell, 2014

“China’s CRISPR twins: A time line of news”, MIT Technology Review, 2019

“p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells”, Ihry et al. Nature Medicine, 2018

“CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response”, Haapaniemi et al. Nature Medicine, 2018

“CRISPR/Cas9 can mediate high-efficiency off-target mutations in mice in vivo” Aryal et al. Cell Death and Disease 2018

CRISPR doc 'Human Nature' embraces the hope and peril of gene editing, Devindra Hardawar, Engadget, March 11, 2019