Gene Therapy Set to Transform Treatment Landscape in Singapore by 2030s

Gene therapy is poised to revolutionize the treatment of genetic diseases in Singapore, with the possibility of mainstream applications emerging by the 2030s. Medical researchers in the country are engaged in pioneering studies focusing on gene editing techniques to address conditions such as heart diseases and blood disorders. A significant area of research includes potential treatments for fetuses in utero, aiming to correct genetic mutations before diseases manifest.

One notable example is transthyretin amyloid cardiomyopathy, a rare genetic heart condition that currently lacks an effective cure. Gene therapy presents a promising avenue for these patients. Scientists in Singapore are conducting trials using the CRISPR-Cas9 gene editing technology on adult patients with heart issues, aiming to rectify genetic defects. Should these trials succeed, it would represent Singapore’s first commercial application of this innovative technology in humans.

Assistant Professor Lin Weiqin, clinical director at the National University Heart Centre Singapore’s Heart Failure and Cardiomyopathy Programme, expressed enthusiasm about the potential impacts. “It is groundbreaking, it is exciting, and it might pave the way for future gene editing trials for other conditions,” he noted, highlighting that this could extend to widely prevalent issues like high cholesterol, hypertension, obesity, and diabetes. The current study is expected to conclude in three to four years, with gene therapy potentially becoming a standard treatment option by the early 2030s.

The CRISPR-Cas9 technology, originally derived from a natural defense mechanism in bacteria against viruses, allows scientists to edit DNA with precision. The process begins with identifying the specific DNA sequence to modify, followed by designing a “guide RNA” that directs the Cas9 protein to the exact location in the DNA strand. The Cas9 enzyme then acts as molecular scissors, creating a cut in the DNA. This triggers the cell’s natural repair mechanisms, which can lead to the gene being rendered nonfunctional. By introducing a template strand of DNA, researchers can guide the repair process to either correct a defective gene or insert a new one. This technique opens the door to targeting nearly any gene in the human genome, including those linked to various diseases.

Advancing Research into Early Interventions

In addition to adult treatments, researchers are exploring the feasibility of addressing genetic disorders at earlier life stages, including before birth. Citra Mattar, a senior maternal-fetal medicine consultant at the National University Hospital’s Department of Obstetrics & Gynaecology, emphasized the potential for more effective therapeutic outcomes when interventions occur before the onset of disease. “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 explained.

Despite the promise of gene therapy, researchers caution that participants in early-stage trials must be aware of the largely irreversible nature of these treatments and the uncertainty surrounding long-term side effects. In cases involving in-utero gene therapy, there are also potential risks for the mother during the treatment process, which are currently under investigation.

Addressing Ethical Considerations

As advances in gene editing unfold, ethical considerations are at the forefront of discussions among scientists and bioethicists. The Bioethics Advisory Committee (BAC) in Singapore recently issued new guidelines emphasizing the importance of ethical safeguards in gene editing practices. Among their recommendations is the stipulation that embryos used for research should not develop beyond 14 days, as this is when they begin to exhibit more human-like characteristics.

Assistant Professor G Owen Schaefer from the National University of Singapore’s Centre for Biomedical Ethics highlighted the potential risks associated with germline editing, which could affect future generations. “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,” he stated. Schaefer advocates for reliance on established methods to mitigate inherited genetic diseases until gene editing technologies are more advanced and reliable.

These discussions underscore the necessity for a balanced approach to gene therapy, where the excitement of scientific progress is tempered by a commitment to ethical standards and patient safety. As Singapore moves forward with its gene therapy research, the implications for healthcare could be profound, marking a new chapter in the fight against genetic diseases.