- Gene “editing” — modifying or rewriting the code of life — has taken a serious step forward.
- Exciting new gene editing techniques ushering in “precision medicine”.
- Using gene editing to redirect the immune system in order to fight diseases is a new field in medicine.
- Concerns had been raised about potential risks, downsides of runaway tampering with DNA.
It's an exciting new field.
Certain types of cancers, heart disease, blindness and spinal muscular atrophy had been reportedly cured in animal models using gene or genome or base "editing" techniques. Potentially, these trials could be used in future gene editing-based approach to treating diseases in humans.
There's a more controversial claim: the delivery of “designer babies” using the latest CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene editing tool.
Together, these new tools that tweak life at the DNA level promise significant contributions to food security, environmental conservation, and scientific understanding. More importantly, they offer huge potential for human health.
In some animal models (rodents), therapeutic advantages for certain types of blindness have been successfully achieved, according to the US National Institutes of Health (NIH).
A Harvard team also used base editing in vivo into two mouse models, which resulted in “30-80% correction of Myh6 transcripts”, exclusively made in cardiomyocytes.
In a report published in February 2023 in the journal Nature Medicine, researchers stated the technique could potentially correct a common mutation that causes hypertrophic cardiomyopathy (HCM), a heart disease that occurs in about 1 in 500 people.
On March 28, 2023, Vertex Pharmaceuticals and CRISPR Therapeutics announced an agreement for the use of gene editing technology to accelerate the development of hypo-immune cell therapies for Type 1 diabetes.
There’s more. In November 2018, a 38-year-old scientist who trained in China and the US announced the birth of twin girls known by their pseudonyms — "Lulu" and "Nana". They were the first people to have their genomes modified by CRISPR.
It was claimed that the researcher modified a gene o give an embryo HIV resistance. The designer baby's embryo had been carried to term. The identical anonymous couple also gave birth to a second child, who reportedly did not have the changed gene.
Revelation kicks up concerns
The revelation has kicked up concerns, but many developments have emerged since then.
Researchers at the Scheie Eye Institute in the Perelman School of Medicine at the University of Pennsylvania have used to technique to treat a genetic form of childhood-onset blindness, allowing the recovery of night vision within days of receiving an experimental gene therapy.
In July 2022, 13-year-old Alyssa from Leicester, became the first person in the world to get base-edited cell therapy as part of a UK clinical trial, after all other treatments for T-cell acute lymphoblastic leukemia had failed. The teenage girl's "incurable cancer" was cleared from her body using genetically-engineered immune cells known as CAR T-cells.
Some notable breakthroughs in gene editing:
CRISPR-Cas9: The development of CRISPR-Cas9 (discovered in 2012), a highly precise and efficient gene editing tool, has revolutionised gene editing, and is used to edit the genomes of a wide range of organisms, from bacteria to humans, with the potential to be used for a wide range of applications, including research, drug development, and gene therapy.
Curing genetic diseases: In 2017, scientists used CRISPR-Cas9 to cure a genetic disease called Duchenne muscular dystrophy in mice. This was the first time that a genetic disease had been cured in an adult animal model using gene editing.
HIV resistance: In 2018, scientists used CRISPR-Cas9 to genetically modify the immune cells of two HIV-positive patients in a clinical trial. The modified cells were able to resist HIV infection and showed no harmful side effects.
Genetically modified crops: Gene editing has also been used to develop crops that are more resistant to pests and diseases, can tolerate extreme weather conditions, and have higher yields. In 2019, scientists used CRISPR-Cas9 to create a tomato plant that was more resistant to a bacterial infection.
Gene therapies: Gene editing has the potential to revolutionise the field of gene therapy, which involves treating diseases by modifying the DNA of affected cells. In 2019, the US Food and Drug Administration approved the first gene therapy based on gene editing, called Luxturna, for the treatment of a rare inherited eye disorder.
Concerns over tweaking DNA
Will changing genetic features of humans cause long-lasting alterations? What repercussions does it pose for the future of humanity? These are questions being asked today as little is yet known about genetic modification for it to be applied to live human subjects.
These are not a new concerns.
The question surrounding the morality — and wisdom — of tampering with the most fundamental components of life first emerged in the 1990s, with the first gene editing technique known as zinc finger nucleases (ZFNs).
The first gene editing technique, called zinc finger nucleases (ZFNs), was developed in the 1990s by a team of scientists from Sangamo Biosciences. However, ZFNs were difficult to design and use, and were not widely adopted.
The breakthrough in gene editing came in 2012 with the discovery of the CRISPR-Cas9 system by Jennifer Doudna and Emmanuelle Charpentier. Another team led by Feng Zhang of the Broad Institute of MIT and Harvard also claim to have developed a similar technology.
A more fundamental concern, however, is that CRISPR-Cas9 itself is not a perfect tool, one study shows it could trigger genetic damage.
◘ CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats): These are short DNA sequences that are found in the genomes of many bacteria and archaea. They serve as a kind of genetic memory, allowing bacteria to recognize and defend against invading viruses.
◘ Cas9 (CRISPR-associated protein 9): This is a protein that can cut DNA at specific locations. Cas9 is guided to the target DNA sequence by a small RNA molecule called a guide RNA (gRNA), which is designed to match the sequence of the target gene.
With gene editing, biologists have found a powerful tool to alter any organism’s “genome” — the complete set of genetic material of an organism, which includes all of its DNA.
"Organism" includes human beings. So now, any biologist who knows gene editing techniques could, in theory, alter human genome. With CRISPR/Cas9, virtually any scientist may modify DNA in almost any cell. Thus, calls for self-regulation are rising.
There are potential downsides including, including safety and ethical concerns:
#1. Off-target effects: Gene editing can lead to unintended and unpredictable changes to the genome, which may have negative consequences. For example, editing one gene may inadvertently affect other genes, leading to unintended effects on the organism.
#2. Ethical concerns: There are ethical concerns surrounding gene editing, particularly when it comes to editing the germline (the DNA passed on to future generations). Editing the germline could be used to create "designer babies," which could lead to eugenic practices and exacerbate existing inequalities.
#3. Safety concerns: Gene editing poses safety concerns, especially when used in humans. The long-term effects of gene editing on human health are not yet fully understood, and there are concerns about potential unintended consequences.
◘ DNA, or deoxyribonucleic acid, is the molecule that encodes the genetic instructions for the development, function, and reproduction of all living organisms.
◘ The genome is made up of long strands of DNA that are organised into discrete units called chromosomes. The size and complexity of a genome vary widely between species.
◘ While organisms, such as viruses and bacteria, have relatively small genomes consisting of just a few thousand base pairs of DNA, the human genome consists of over 3 billion base pairs and is spread across 23 pairs of chromosomes.
Why is the study of genomes important?
In general, understanding the structure and function of genomes can provide insights into the evolution of species, the causes of genetic diseases, and potential targets for drug development.
Advances in sequencing technology have made it possible to rapidly sequence and analyse the genomes of many different organisms, providing a wealth of new data for researchers to explore.
Gene editing vs genome editing vs base editing: What’s the difference?
Gene editing, genome and base editing editing are often used interchangeably, but there are a subtle differences.
Gene editing is a process where the DNA sequence of a gene is changed or modified to produce a desired effect. It refers specifically to the process of making changes — adding, deleting, replacing specific sections of genetic material — or set of genes within an organism's DNA, in order to produce a desired effect.
Genome editing involves making changes to the entire genome of an organism, rather than just a specific gene or set of genes. This can involve modifying multiple genes or even entire chromosomes.
Base editing is a more precise and targeted method of altering DNA. Rather than cutting and pasting DNA, base editing involves changing/editing individual nucleotides, the building blocks of DNA. This technique can be used to correct specific genetic mutations that cause diseases, such as sickle cell anemia or cystic fibrosis.
Base editing is currently limited to making certain types of changes, and it may not be suitable for all types of genetic modifications.
At the moment, potential benefits include applications in agriculture/developing crop resistance, medicine/treatment disease, treating genetic diseases — such as:
- Sickle cell anaemia
- Cystic fibrosis
- Huntington's disease
- Certain types of blindness
- Type 1 diabetes
- Certain cancers
- Spinal muscular atrophy
What are the leading scientific papers on gene editing?
Some key papers in the field include:
#1. ”CRISPR/Cas9-mediated genome editing and gene replacement in plants: Transitioning from lab to field" by Qiwei Shan, Heng Zhang, and Caixia Gao (2019). This review paper discusses the use of CRISPR/Cas9 for gene editing in plants and the potential applications for agriculture.
#2. “CRISPR-Cas9: from a bacterial immune system to genome-edited humans" by Jennifer Doudna and Emmanuelle Charpentier (2014). This paper describes the development of the CRISPR/Cas9 gene editing system and its potential for use in humans.
#3. “Precise base editing in rice, wheat and maize with a Cas9-cytidine deaminase fusion" by Lei Li et al. (2021). This paper describes a new CRISPR-based gene editing system that allows for precise changes to individual DNA bases in crops.
#4. “Germline editing and the future of the human species" by Jennifer Doudna and Samuel Sternberg (2017). This paper explores the ethical considerations surrounding gene editing in humans and the potential implications for future generations.
We're entering a new era in genome engineering. It's nothing less than a revolution. Gene editing, in general, is a great tool. It won't be a big surprise if investors, including Big Tech, would pour money into it. Yet it's nowhere near perfection.
Since CRISPR-Cas9’s discovery, other gene editing tools and techniques have also been developed, including TALENs and "prime editing", which offer additional capabilities and advantages over CRISPR-Cas9 in certain contexts.
As with any great power, it comes with great responsibility. Those who are in this field need to use it with great care.
Would altering genetic traits lead to permanent changes for humanity as a whole?
Only time will tell.