Gene Therapy Advances in Singapore: Hope and Ethical Dilemmas

In Singapore, medical researchers are making significant strides in gene therapy, with the potential for mainstream treatments for genetic diseases by the 2030s. This emerging field aims to address conditions such as heart diseases and blood disorders, offering hope to patients who currently have limited options. Notably, scientists are exploring gene editing methods that could even treat foetuses in the womb.

One focus of current research is transthyretin amyloid cardiomyopathy, a rare genetic heart ailment with no existing cure. Researchers at the National University Heart Centre Singapore are conducting gene editing trials on adults with heart conditions, aiming to correct genetic defects at their source. If successful, this could represent the first commercial application of CRISPR-Cas9, a powerful gene editing technology, in Singapore.

Advancements and Potential Applications

Assistant Professor Lin Weiqin, clinical director of the Heart Failure and Cardiomyopathy Programme, describes the research as “groundbreaking” and anticipates it could lead to further gene editing trials for more prevalent conditions such as high cholesterol, hypertension, obesity, and diabetes. He estimates that the study will take an additional three to four years to complete.

The CRISPR-Cas9 technology, adapted from a natural defense system used by bacteria against viruses, has primarily been applied to blood cancers and paediatric neuromuscular diseases. The process begins with identifying the DNA sequence that needs alteration. A guide RNA is crafted and attached to the Cas9 protein, directing it to the specific location in the DNA. The protein then acts as molecular scissors, cutting the DNA strand. Following this, the cell attempts to repair the break, which may result in an unusable gene. To address this, scientists introduce a template DNA sequence to guide the reconstruction process, potentially repairing defective genes or inserting new ones. This method allows for targeting nearly any gene linked to diseases.

Ethical Considerations and Guidelines

Despite the promise of gene therapy, ethical concerns persist. The Bioethics Advisory Committee (BAC) of Singapore has released new guidelines, urging that embryos used for research should not develop beyond 14 days. This timeframe aligns with when embryos begin to exhibit a more “human-like” structure, raising ethical, social, and legal issues.

Associate Professor Citra Mattar, a senior maternal fetal medicine consultant at the National University Hospital, emphasizes the importance of correcting abnormal gene mutations early, ideally before disease onset. “When the recipient is well, we can expect the therapeutic outcomes to be better,” she states, noting that the effectiveness of treatment may diminish if the patient already carries a substantial disease burden.

Nonetheless, researchers caution that patients participating in early-stage trials need to be aware that gene therapy is largely irreversible, and long-term side effects are still uncertain. The risks of in-utero gene therapy may also extend to mothers, a factor that continues to be investigated.

Assistant Professor G. Owen Schaefer from the National University of Singapore’s Centre for Biomedical Ethics highlights the potential risks of inheritable gene editing. “If something goes wrong, it doesn’t just affect that particular individual,” he warns, stressing the importance of utilizing established methods to mitigate the risk of genetic diseases until gene editing technologies are more reliable.

As Singapore navigates the complex landscape of gene therapy, balancing innovation and ethical responsibility will be crucial to ensure that advancements serve the best interests of patients and society at large.