The obstacle facing antibodies is an electrical one. That is the conclusion sitting at the heart of new research from the University of Essex, and it goes a long way toward explaining why decades of antibody development has largely stalled at the cell membrane.
Working alongside an international team, the Essex researchers turned to artificial intelligence to design exceptionally small antibody fragments that human cells can manufacture internally. Once there, those fragments are able to bind to proteins linked with disease.
Conventional antibodies tend to operate outside the cell. These reworked fragments — known as intrabodies — are instead built to stay stable within it, which brings them within reach of the proteins implicated in neurodegenerative conditions.
The barrier was charge, not shape
Funding came from the MND Association, with Dr. Caitlin O’Shea and Dr. Gareth Wright of the School of Life Sciences leading the project. What the team established is that electrical charge is a key factor in whether an antibody fragment remains stable and functional once it is inside a cell.
Combine that insight with AI-led protein redesign and what emerges is a hard number rather than a promise. The researchers converted 672 different antibodies into intrabodies capable of targeting important disease-related proteins.
By acting directly within living cells — where many of the biological processes behind these conditions begin — the method could hand scientists new ways to study and potentially treat neurodegenerative diseases.
Following publication in Nature Communications, the redesigned molecules will be released freely to other scientists. That detail carries more weight than it first appears. Free availability means other labs can put the claim to the test rather than accept it on faith.
How the team worked it out
O’Shea, the lead author, specializes in MND and Parkinson’s disease. She said: “We looked at the properties of millions of antibodies and compared them with human proteins found inside the cell.
“From this we figured out that antibodies usually have the wrong charge to exist inside cells without sticking together.
“We used software developed by Nobel Prize winner David Baker and his group to redesign our antibody fragments, so they had the right charge and are super stable.”
New roles for millions of existing antibodies
In the researchers’ view, the findings could allow scientists to identify fresh uses for the millions of antibodies developed over decades of biomedical research.
Rather than beginning from zero, antibodies that already exist may be adaptable into laboratory tools and, potentially, the basis for future treatments aimed at disease-causing proteins. That word “potentially” is carrying genuine weight, and the researchers make no attempt to disguise it.
Wright, who directed the research, said the approach could have major implications for diseases affecting tens of millions of people worldwide.
“We’ve made intracellular antibodies that stick to proteins that cause neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and motor neurone disease,” said Wright.
“These diseases can lead to cognitive impairment, forgetfulness, loss of muscle control and death. They affect over one million people in the UK alone, so they are a big public health concern.
“There are no cures for these diseases and finding molecules that interact with the proteins that cause them in their native environment is a major challenge in the medicine discovery process.”
What the funder says — and what it stops short of saying
The MND Association welcomed the results and highlighted what they might mean for future treatments. Read the charity’s wording closely, though, and the hedging is hard to miss.
Dr. Brian Dickie, chief scientist at the charity, said: “Dr. Wright and his colleagues have made a significant advance in overcoming one of the key challenges that has impeded the development of antibodies as treatments for neurodegenerative diseases, such as MND.
“Their research findings provide optimism that a combination of this novel ‘intrabody’ science with emerging gene therapy techniques may lead to new therapeutic strategies that can hit specific molecular targets within neurones.”
May lead. Emerging gene therapy techniques. Those are the phrases doing the heavy lifting here, and to the charity’s credit they are the honest ones. Nobody involved is announcing a treatment.
If one figure from this work is worth holding onto, make it 672. That is how many antibodies crossed from outside the cell to inside it, and every one of them is about to land in the hands of other researchers.