Researchers will develop a new gene therapy platform designed to correct hundreds of rare blood and immune disorders caused by single-letter DNA mutations, thanks to a $5 million Medical Research Future Fund grant.
More than 600 distinct blood and immune diseases are caused by tiny errors in the genetic code within blood stem cells. These conditions are rare but often severe and life-limiting, and collectively affect millions of people worldwide.
The WEHI-led project will use a lab-grown 'patient avatar' developed from individual blood samples to create a faster, safer path to treatment, alongside a regulatory blueprint that helps personalised gene therapies reach patients who are currently left behind.
At a glance
• A WEHI-led project has received a $5 million Medical Research Future Fund (MRFF) grant to develop a personalised gene therapy platform for rare blood and immune diseases.
• The approach combines a blood-based 'patient avatar' in the lab with cutting-edge prime editing technology to precisely repair disease-causing DNA changes.
• The team will work with research partners across the Peter MacCallum Cancer Centre (Peter Mac), the Royal Melbourne Hospital (RMH) and the Royal Children's Hospital (RCH) to develop a platform approach for personalised therapies and reduce the regulatory bottleneck for bespoke treatments designed for small patient groups.
A disease model in a dish
For many rare blood and immune disorders, getting a clear diagnosis can take months or years. Even when a diagnosis is found, the only curative option for many patients is a transplant of stem cells from a healthy donor - an intensive treatment that can be risky, toxic, expensive and often inaccessible.
WEHI researchers have developed a 'blood in a dish' system that uses stem cells collected from a patient's blood sample to recreate key parts of blood and immune development outside the body.
This patient avatar allows researchers to see what's going wrong for individual patients and to test whether a specific genetic fix can restore normal function.
Project chief investigator Professor Shalin Naik said the approach is designed to make personalised medicine practical for diseases that have never attracted large-scale investment.
"Many of these conditions come down to a single-letter genetic mutation, but the exact mutation can differ from patient to patient," Prof Naik, a WEHI laboratory head, said.
"Our system lets us model a patient's disease in the lab, test a precise correction and measure whether the cells bounce back."
The project uses cutting-edge prime editing technology that allows scientists to precisely change one DNA 'letter' for clean, targeted repair.
"That specificity is what makes prime editing so exciting for rare diseases and makes this project such a potential game changer for diseases that are crying out for effective, tailored treatments," said Prof Naik.
The project will package prime editing components as mRNA inside lipid nanoparticles - the same broad class of delivery technology used for mRNA vaccines, like those for COVID-19 - and direct them to blood stem cells in the bone marrow.
Lab proof leads to real-world treatment
Matthew Rozek was diagnosed at birth with SCID, a rare inherited immune disorder that left him vulnerable to serious infections from infancy. He spent much of his childhood in hospital and has lived ever since with ongoing treatment, repeated infections and the knowledge that even minor illness can quickly become serious.
"It's a constant impact on your quality of life, and at any point you can get sick and it becomes a crisis," Matthew said.
Using Matthew's stem cells, the WEHI team has already shown proof-of-concept for the project, correcting the SCID-causing mutation and restoring immune cell development in the lab.
However, when it came time for treatment, he had to travel overseas because no equivalent option existed here.
In 2025 Matthew received an experimental gene therapy through a clinical trial in the US. His treating clinician at the RMH, Dr Samantha Chan, said that the stakes were critical.
"We sent him to the US because we thought he would die if he didn't get treatment," said Dr Chan, who is Deputy Director of Clinical Immunology and Allergy at the hospital, Immunodeficiency Lead for the Department of Infectious Diseases & Immunology at Austin Health, immunology and allergy clinician-scientist for the Snow Centre for Immune Health, a WEHI researcher and a chief investigator on the project.
Dr Chan said that while the treatment was intensive, early signs have been encouraging and she's hopeful Matthew will be able to lead a relatively normal life.
"We need treatments like this here in Australia, because not every patient can travel overseas and not every patient can afford to wait. For patients like Matthew, waiting can mean more infections, more complications and reaching a point where treatment is no longer possible."
Matthew hopes research like this will make it possible for people with rare immune disorders to access faster, safer and more tailored treatments in future.
"If you can treat this when someone is very young, they don't have to go through years of suffering first," he said.
From 'one disease, one therapy' to a scalable platform
Even as genetic therapies advance, rare diseases have often been left behind. Many conditions affect only a small number of people making it difficult to develop and bring to market a single commercial product.
The project team will work with hospitals, consumers and regulators to design a platform approach for personalised therapies: a consistent process with strict safety and efficacy benchmarks, where the outcome can be adapted to each patient.
WEHI researcher Dr Thomas Lew said the combination of lab-based screening, targeted delivery and a platform approach could shorten the time between diagnosis and treatment, while reducing risk for patients.
"We want to build a unified gene therapy platform that can deliver cures for as many patients has possible - from a child born with an incurable mutation to an adult that has developed one in their lifetime," said Dr Lew, who is also a clinical haematologist at Peter Mac and the RMH.
"Importantly, this project has the bold but critical goal of transforming regulatory approaches that have been a barrier to getting these new and effective treatments quickly and safely to patients."
Prof Naik said that the project seeks to shift the regulatory status quo of 'one treatment, one disease'.
"To reach patients with rare diseases we need a platform pathway with strict safety benchmarks, so we can shorten the long road from diagnosis to personalised treatment."
Over the five-year MRFF Stem Cell Therapies Mission Stream 1 program, the team aims to deliver a Phase I clinical trial-ready package, including manufacturing and safety testing. Further investment and support will be needed to progress the project through clinical trials at scale.
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About WEHI (Walter and Eliza Hall Institute of Medical Research) WEHI is where brilliant minds collaborate and innovate to make life-changing scientific discoveries that help people live healthier for longer. Our medical researchers have been serving the community for more than 100 years, making transformative discoveries in cancer, infection and immunity, and lifelong health. WEHI brings together diverse and creative people with different experience and expertise to solve some of the world's most complex health problems. With partners across science, health, government, industry, and philanthropy, we are committed to long-term discovery, collaboration, and translation. At WEHI, we are brighter together.
