Gene Therapy Advances in Singapore Aim for Mainstream Use by 2030s

Singapore is at the forefront of gene therapy research, with the potential for mainstream applications in the treatment of genetic diseases by the 2030s. Medical researchers are actively exploring gene editing techniques for various conditions, including heart ailments and blood disorders, and are even examining treatments for foetuses in utero.

One of the significant advances in this field is the application of gene therapy to address transthyretin amyloid cardiomyopathy, a rare genetic heart disease that currently has no cure. Researchers at the National University Heart Centre Singapore are conducting trials using gene editing to correct genetic defects in adult patients. If successful, this could represent Singapore’s first commercial use of the CRISPR-Cas9 technology on humans.

Assistant Professor Lin Weiqin, clinical director of the Heart Failure and Cardiomyopathy Programme, described the ongoing work as “groundbreaking” and expressed optimism about its implications for treating more common conditions such as high cholesterol, hypertension, obesity, and diabetes. He indicated that the study is approximately three to four years from completion, setting the stage for wider gene therapy applications.

The CRISPR-Cas9 system, originally derived from a natural defense mechanism in bacteria, has emerged as a powerful tool for editing DNA. It allows scientists to target specific DNA sequences by employing a “guide RNA” that directs the Cas9 protein to the precise location in the genome. Once there, the protein acts as a pair of molecular scissors, cutting the DNA. The cell then initiates a repair process that can either restore normal function or introduce new genetic material.

While the potential for gene therapy is vast, researchers are also investigating early interventions. Associate Professor Citra Mattar from the National University Hospital’s Department of Obstetrics & Gynaecology highlighted the importance of correcting genetic mutations in foetuses before the onset of disease. She noted that intervening while the recipient is healthy can lead to better therapeutic outcomes compared to treating individuals who already have significant disease burdens.

Despite these promising developments, there are notable risks associated with gene therapy. Patients entering early-stage trials must acknowledge the largely irreversible nature of these treatments, and long-term side effects remain uncertain. For in-utero therapies, potential complications for mothers during the treatment process are also under investigation.

Ethical Considerations in Gene Therapy Research

As gene editing technology progresses, ethical concerns have come to the forefront. The Bioethics Advisory Committee (BAC) of Singapore recently released guidelines urging researchers to implement strong safeguards as they explore gene editing capabilities. Among the recommendations is a restriction on the development of embryos used in research beyond 14 days, due to ethical, social, and legal implications.

At this stage of development, embryos begin to exhibit more “human-like” characteristics, raising significant ethical questions. Assistant Professor G Owen Schaefer from the National University of Singapore’s Centre for Biomedical Ethics cautioned against editing genes that could be passed down to future generations, highlighting the unpredictable outcomes such actions may entail. He advised reliance on established methods for preventing inherited genetic diseases while awaiting advancements in gene editing technology.

Scholars emphasize the necessity of prudent practices in this rapidly evolving field, urging researchers to prioritize established techniques until gene editing is more mature and reliable. The dialogue surrounding the ethical implications of gene therapy will continue as Singapore positions itself at the cutting edge of this transformative medical frontier.