Gene Therapy Set to Revolutionize Treatment in Singapore by 2030

Gene therapy is on track to become a pivotal treatment option for patients with genetic diseases in Singapore by the 2030s. Researchers in the nation are actively investigating gene editing techniques to address various health issues, including heart conditions and blood disorders. Notably, trials are underway to explore the potential of treating foetuses in the womb, marking a significant advancement in the field.

One specific challenge is transthyretin amyloid cardiomyopathy, a rare genetic heart disease currently lacking an effective cure. In response, scientists in Singapore are conducting clinical trials involving gene editing on adult patients. If successful, these trials could introduce the first commercial use of CRISPR-Cas9, a cutting-edge gene editing technology, on human subjects.

Assistant Professor Lin Weiqin, the clinical director of the National University Heart Centre Singapore’s Heart Failure and Cardiomyopathy Programme, described the research as “groundbreaking” and expressed optimism about its implications. He mentioned that successful gene therapy could eventually extend to common health issues such as high cholesterol, hypertension, obesity, and diabetes. The study is projected to take three to four years to complete, yet the potential for mainstream adoption looms large within the next decade.

Understanding CRISPR-Cas9 and Its Applications

The CRISPR-Cas9 technology, originally derived from a natural genome-editing system used by bacteria to fend off viruses, is now a powerful tool for altering DNA. The process begins with identifying the specific DNA sequence targeted for modification. A guide RNA is created and paired with the Cas9 protein, directing it to the precise location in the DNA strand. The Cas9 protein then acts like molecular scissors, cutting the DNA. Following this incision, the cell’s natural repair mechanism kicks in, attempting to mend the break.

However, this repair can lead to unusable genes, which is why scientists introduce a separate template of DNA. This blueprint aids in the rebuilding process, allowing for the correction of defective genes or the insertion of new ones. This innovative technique enables targeting nearly any gene within the genome, including those linked to various diseases. Despite its promise, researchers continue to evaluate the long-term effects of this technology on human health.

Researchers are also delving into the possibility of administering gene therapy at earlier life stages, including before birth. Associate Professor Citra Mattar, a senior maternal fetal medicine consultant at the National University Hospital’s Department of Obstetrics and Gynaecology, emphasized the benefits of correcting abnormal gene mutations in a child or foetus prior to disease onset. “When the recipient is well, we can expect the therapeutic outcomes to be better compared to when a person already has a lot of the disease burden,” she stated.

Despite the potential advantages, researchers caution that participants in early-stage trials must be fully aware of the largely irreversible nature of gene therapy and the uncertainty surrounding long-term side effects. For instance, maternal side effects may arise during in-utero treatment, which is still under investigation.

Ethical Considerations in Gene Editing

As advancements in gene editing accelerate, ethical experts are urging for caution. The Bioethics Advisory Committee (BAC) in Singapore has recently published guidelines addressing the ethical implications of such technologies. During a conference last week, the BAC advised that embryos used for research should not develop beyond 14 days. This recommendation stems from ethical, social, and legal considerations, as embryos begin to exhibit more human-like characteristics at this stage.

Furthermore, the BAC discourages editing genes in ways that may affect future generations, highlighting the unpredictable consequences that could arise. Assistant Professor G Owen Schaefer from the National University of Singapore’s Centre for Biomedical Ethics articulated the potential risks involved. He noted that any modifications made to embryos or gametes (sperm and egg) could have repercussions for future descendants. “If something goes wrong, it doesn’t just affect that particular individual. If they go on to have children, it will affect future generations in ways we cannot accurately predict,” Schaefer warned.

He advised sticking to established methods for reducing the risk of inherited genetic diseases until gene editing technology becomes more reliable and advanced. “It’s better to stick with the more certain, safer methods and wait until the science is more mature before proceeding with riskier approaches at the embryonic level,” he concluded.

As Singapore moves closer to integrating gene therapy into mainstream medical practice, the balance between innovation and ethical responsibility will be crucial in shaping the future of healthcare in the region.