For decades the backbone of modern medicine has been small-molecule drug- and biologic-based interventions. These conventional approaches have saved countless lives, but they come with significant trade-offs: limited precision, systemic side effects, and low efficacy for some medical conditions.

This is where nature offers both inspiration and instruction. Across millions of years, biological systems have evolved exquisitely targeted mechanisms to interact with cells, tissues, and environments in ways modern medicine is only beginning to replicate.

Today, researchers are borrowing from nature’s playbook and emulating nature’s targeting strategies. To do this researchers are reengineering biology and unlocking transformative therapies.

At NUS, scientists are developing programmable microbes to produce valuable compounds, engineered probiotics for brain-targeted delivery, and non-viral platforms for precise gene editing in immune cells.

Microbes as mini factories

Ergot fungus has long been used to produce D‑lysergic acid (DLA), a key precursor in medications for dementia, Parkinson’s disease, migraines, and other neurological conditions. However, traditional methods of cultivation are slow, resource-intensive, and difficult to scale.

In a collaborative project between NUS Medicine and Imperial College London, Associate Professor Yew Wen Shan and his team programmed baker’s yeast (Saccharomyces cerevisiae) with synthetic genes from the ergot fungus to produce DLA sustainably. Within just a day or two of fermentation in a bioreactor, the engineered yeast generated small but scalable amounts of DLA, approximately 1 to 5 mg per litre, with the potential for multi-tonne annual production. Unlike conventional ergot cultivation, which requires large areas of land and careful fungal management to produce DLA, this approach offers a more sustainable and scalable microbial platform.

Delivering medicine across the blood-brain barrier

Beyond fungus, commensal bacteria, microorganisms that naturally reside in the human body without causing harm, are also being reprogrammed to act as therapeutic allies to challenge the blood-brain barrier. One of medicine’s most formidable challenges, this barrier blocks the vast majority of drugs from entering the central nervous system, excluding nearly 98% of potential drug candidates for neurological disease treatments. To overcome this, NUS scientists, led by Dr Haosheng Shen from the Synthetic Biology Translational Research Programme, engineered Lactobacillus plantarum. The team enabled targeted, efficient transport of drugs, potentially reducing systemic side effects while increasing treatment precision.

Safer, more precise immune therapies

Even our own cells are providing a powerful template to revolutionise the human immune system. T cells, a type of lymphocyte, or white blood cell, already know how to recognise and eliminate diseased cells. CAR-T cell therapy builds on this natural intelligence by genetically programming a patient’s T cells with synthetic receptors that precisely target cancer cells – turning them into personalised, living therapies capable of evolving alongside disease.

However, current CAR-T cell therapy faces major challenges. Delivering genetic material into immune cells without any compromise is inherently difficult. Current industry-standard methods include viral vectors and bulk electroporation. Viral vectors are effective but pose safety risks, including immunogenicity and random gene integration. Bulk electroporation, on the other hand, uses high-voltage pulses that can damage cells and reduce therapeutic quality. In Singapore, a single CAR-T treatment can cost around S$670,000, an astronomical amount for general patients, even with subsidies.

NUS researchers, led by Assistant Professor Andy Tay, tackled this challenge with the Nanostraw Electro-actuated Transfection (NExT) platform, a non-viral system that enables rapid, precise gene transfer into even the hardest-to-engineer immune cells, from macrophages to gamma-delta T cells. By creating tiny “nanostraw” conduits that gently introduce genetic material into cells while minimising stress and damage, NExT preserves cell viability, improves efficiency, and allows researchers to fine-tune cellular functions with unprecedented control. The team is now validating the technology in preclinical studies while partnering with industry to integrate it into existing manufacturing workflows and explore real-world applications.

Today, medicine is no longer just a response to disease – it is a collaboration between human ingenuity in engineered biological systems and the wisdom embedded in nature over the course of evolution.