The Growing Challenge of Inherited Retinal Diseases in Singapore

Inherited retinal diseases (IRDs), a group of rare genetic disorders that progressively damage the retina—the light-sensitive tissue at the back of the eye—pose a significant health burden worldwide, including in Singapore. These conditions, such as retinitis pigmentosa (RP), Stargardt disease, and Leber congenital amaurosis, lead to gradual vision loss, often resulting in legal blindness by middle age. In Singapore, the prevalence of RP alone is approximately 0.06% based on population studies, with carrier rates for specific mutations like EYS C2139Y reaching 0.66% among Chinese Singaporeans. While exact IRD figures vary due to Singapore's multi-ethnic population, economic analyses estimate substantial costs, including direct medical expenses and indirect productivity losses, underscoring the urgency for innovative therapies.

Current treatments are limited; options like vitamin A supplementation for RP offer modest delays in progression, but gene therapies like Luxturna (for RPE65 mutations) remain unavailable locally and target only a fraction of cases. This gap highlights the need for versatile, precision approaches like those pioneered by researchers at A*STAR.

Meet Dr. Beverly Mok: A Rising Star in Synthetic Biology

Dr. Beverly Mok, Senior Scientist at A*STAR's Institute of Molecular and Cell Biology (IMCB), embodies Singapore's drive toward biotech excellence. Trained as a synthetic biologist with a PhD in Chemistry and Chemical Biology from Harvard University (2021), Dr. Mok transitioned from postdoctoral work to leading cutting-edge projects at IMCB's Molecular Engineering Laboratory. Her journey began with a passion for genetic diseases, sparked during her doctoral research on mitochondrial base editors—tools that enable precise DNA changes without double-strand breaks, reducing off-target risks.

In 2025, Dr. Mok received the prestigious L'Oréal–UNESCO For Women in Science award, recognizing her contributions to RNA-based therapies for IRDs and rare disorders. This accolade not only celebrates her individual achievements but also spotlights A*STAR's role in nurturing global talent. As she notes in interviews, her work bridges fundamental science and clinical translation, leveraging Singapore's robust ecosystem.

Protein Engineering: Crafting Custom Molecular Tools

At the core of Dr. Mok's toolkit is protein engineering, the process of redesigning proteins—nature's workhorses—to perform novel functions. For IRDs, where mutations disrupt retinal proteins like rhodopsin or RPE65, she engineers enzymes such as deaminases (e.g., from DddA toxin) fused to programmable DNA/RNA binders. These chimeric proteins enable site-specific base editing: converting one DNA letter (cytosine C to guanine G) without cutting the genome, minimizing errors.

Building on her Harvard work, Dr. Mok has evolved these editors for higher efficiency and broader targeting. Step-by-step: 1) Identify mutation via sequencing; 2) Design guide RNA/DNA for precision binding; 3) Engineer protein for stability and activity; 4) Test in retinal organoids or animal models. This has yielded editors installing disease mutations in cells for study, paving the way for reversals. Her innovations extend to RNA editing using ADAR enzymes, ideal for transient corrections in non-dividing retinal cells.

For those exploring careers in biotech, Singapore offers opportunities like research jobs at A*STAR, blending academia and industry.

Genome Editing Tailored for the Eye's Unique Environment

The eye's immune privilege—low immune response—and subretinal accessibility make it ideal for gene therapies. Dr. Mok adapts CRISPR-free editors for retinal delivery via adeno-associated viruses (AAVs), nanoparticles, or exosomes. Recent advances include unconstrained mitochondrial editing (αDdCBEs), correcting pathogenic mtDNA mutations in mice models relevant to Leber's Hereditary Optic Neuropathy (LHON), an IRD.

In Singapore, where IRDs affect diverse ethnic groups (Chinese, Malay, Indian), her multi-modal strategies address variable genetics. Collaborations with IMCB's Translational Retinal Research Lab, led by A/Prof. Su Xinyi, model IRDs using patient-derived induced pluripotent stem cells (iPSCs) turned retinal organoids, testing editors pre-clinically.

RNA Strategies: Editing Transcripts for Rapid Therapy

Beyond DNA, Dr. Mok advances RNA editing, replacement, and protein substitution. RNA editing alters mature transcripts temporarily, suiting dynamic retinal needs. Using engineered ADARs, she targets premature stop codons in RP-causing genes like USH2A. RNA replacement delivers corrected mRNA, while protein engineering produces stable retinal proteins for injection.

These platforms, funded by three grants, aim for first-in-human trials. Advantages: reversibility, no genomic integration risks. In lab models, they restore photoreceptor function, delaying degeneration. Singapore's higher education ties, like with NUS and NTU, accelerate vector optimization.

Collaborative Ecosystem at A*STAR and Beyond

Dr. Mok's success stems from IMCB synergies: Cell & Molecular Therapy Division develops delivery vectors, while GIS provides genomic insights. Partnerships with NUHS and SERI enable patient cohorts for validation. Externally, her Harvard roots foster global exchanges.

A*STAR IMCB exemplifies Singapore's RIE2025 plan, investing S$25B in research.

2025 L'Oréal-UNESCO Award: Spotlight on Impact

The award underscores Dr. Mok's trajectory from mtDNA pioneer to IRD leader. As IMCB notes, her RNA platforms could transform rare disease care, leveraging the eye as a 'proof-of-concept' organ. In multi-perspective views, clinicians hail reduced off-targets, ethicists note germline avoidance.

Singapore's Biotech Hub: Fueling IRD Innovation

Singapore ranks high in biotech, with A*STAR bridging universities like NUS Yong Loo Lin School of Medicine. Initiatives like PRECISE-SG10K map IRD genetics. Economic studies peg IRD costs high, justifying investments.

For aspiring researchers, academic CV tips and postdoc jobs abound.

Challenges and Solutions in IRD Therapy Development

• Mutation Diversity: 300+ IRD genes; Solution: Modular editors.
• Delivery Barriers: Retinal layers; Solution: Engineered AAVs.
• Off-Targets: Protein tweaks minimize.
• Regulatory: Singapore HSA fast-tracks.

Future Outlook: Toward Clinical Trials

Dr. Mok eyes IND filings by 2028, with eye therapies leading gene editing approvals. Broader impacts: Brain/muscle disorders. Singapore's vision: Global leader in precision medicine.

Career Paths in Singapore's Gene Therapy Landscape

Inspired? Explore university jobs, faculty positions, or Singapore opportunities. Platforms like Rate My Professor aid decisions.

Photo by Kharl Anthony Paica on Unsplash

Why Dr. Mok's Work Matters for Patients and Science

Her strategies promise restored vision, reducing Singapore's IRD burden. As biotech evolves, A*STAR exemplifies innovation. Stay updated via higher ed career advice and higher ed jobs. For jobs, visit higher-ed-jobs; rate educators at rate-my-professor.