Rewriting The Human Genome

By using emerging gene editing techniques to modify and engineer DNA, Dr Chew Wei Leong and his team at the Genome Institute of Singapore are imagining a world without disease.

Dr Chew Wei Leong, Group Leader and Associate Director at A*STAR’s Genome Institute of Singapore (GIS), has one goal: to rewrite the human genome. It sounds ambitious, but emerging technologies are making gene editing — or the act of adding, removing, or altering particular parts of an organism’s DNA — possible. Doing so allows scientists to develop gene therapies that can treat diseases that were previously thought to be incurable.

In 2016, Dr Chew provided one of the first demonstrations of multi-organ gene editing and genetic disease correction in mice using CRISPR. Initially discovered in bacteria, CRISPR has generated much excitement within the scientific community because it is more versatile, fast, and affordable than other genome editing techniques—thereby opening the door for exactly the type of research Dr Chew and his team have set out to do.

Since then, Dr Chew has accumulated more than 20 patents and technology disclosures in the field of gene editing, gene therapy, and nucleic acid technologies. His team’s research currently covers genome editing, immunology, and gene therapy. They develop technologies that allow for pinpoint alteration of specific genes, delivery of treatments and, ultimately, saving lives.

In this interview, Dr Chew talks about developing the cure for genetic disorders, rewriting the blueprint of life, and what these developments mean for Singapore.

Why should Singapore be excited about research on gene editing and CRISPR from a healthcare angle?

Gene editing is precision surgery on our genomes. This means that genes with mutations that cause diseases could be corrected to the healthy versions within the patients.

Using these new technological breakthroughs, we can now develop therapeutics that permanently cure genetic disorders at the root cause: the gene level. This is an entirely new way to treat and cure diseases, including previously incurable ones, with important implications for patients in Singapore and globally.

On your website, you describe your work as “Rewriting Life.” What research work is the Chew Lab currently focusing on?

Our technologies rewrite DNA, the blueprint of life. In editing DNA, we change how our cells and body function. Gene editing has a universal impact on other lifeforms, not just in therapeutic benefits for humans. Gene editing technology is already impacting diverse human activities, such as agriculture, manufacturing, and environmental control.

Our lab at the Genome Institute of Singapore develops technologies for gene editing, nucleic acid therapeutics, and synthetic biology. Our mission is to make DNA-writing routine medicine for patients at the clinic.

Can you share with us highlights of some research projects geared towards establishing safe and effective genome therapeutics?

We have extensive research experience in understanding the safety profiles of gene editing therapeutics, especially through how our immune system responds to the therapy. Through our work and that of our colleagues, we now know that the most promising gene therapy and gene editing therapy approaches induce strong immune responses that pose safety risks. Importantly, our work has shown that engineered therapeutics can evade these immune responses, allowing many people to benefit from these game-changing medicines.

For more than a decade, we have been on this journey to develop gene editing therapeutics, starting from early predecessors of the gene editing technology such as zinc finger nucleases and TALENs, and subsequently pioneering work in CRISPR-Cas9 technologies. These early successes have built solid foundations for many contemporary therapeutic pipelines, but we continue to innovate in the next generation of technology. Some exciting work involves our base editor technology which allows us to precisely change one letter in the genome to another; gene delivery vectors, which sends the therapeutics precisely into the desired cell targets; and molecular technologies, which enables new and more sophisticated genome engineering applications.

Has any of the research been translated to bedside clinical applications?

Despite their enormous promise, gene editing technologies are still emerging, and clinical trials have only just begun globally. Data from multiple clinical trials have shown promising cures in patients suffering from cancers and blood disorders. We are optimistic that rigorous preclinical studies and clinical trials will soon bring safe and efficacious therapeutics to patients.

What is your vision for Chew Lab from the perspective of Singapore’s National Precision Medicine Programme?

We are extremely excited to understand the genomics of our Singaporean population via the NPM Programme led by Precision Health Research, Singapore (PRECISE). From this valuable knowledge, we would begin the journey of developing groundbreaking therapeutics for genetic diseases that are prevalent in Singaporeans. This would be one of the many impressive health benefits of the NPM Programme to our people.