Working with an international team, the scientists used artificial intelligence to create extremely small antibody fragments that can be produced directly inside human cells. Once there, the fragments can attach to proteins associated with disease.

Ordinary antibodies generally function outside cells. The newly redesigned fragments, called intrabodies, have instead been engineered to remain stable within cells, allowing them to target proteins involved in neurodegenerative conditions.

Electrical Charge Helps Antibodies Survive Inside Cells

The research was funded by the MND Association and led by Dr. Caitlin O’Shea and Dr. Gareth Wright from the School of Life Sciences. The team discovered that electrical charge is a key factor in determining whether antibody fragments can remain stable and functional inside cells.

Using that insight together with AI-powered protein redesign, the researchers converted 672 different antibodies into intrabodies capable of targeting important disease-related proteins.

The advance could give scientists new ways to study and potentially treat neurodegenerative diseases by acting directly inside living cells, where many of the biological processes involved in these conditions begin.

Following publication of the research in Nature Communications, the redesigned molecules will be made freely available to other scientists.

Lead author Dr. O’Shea, who specializes in MND and Parkinson’s disease, 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.”

Repurposing Millions of Existing Antibodies

The researchers believe the findings could allow scientists to find new uses for millions of antibodies developed during decades of biomedical research.

Rather than starting entirely from scratch, existing antibodies may be adaptable for use as powerful laboratory tools and, potentially, as the foundation for future treatments aimed at disease-causing proteins.

Dr. Wright, who directed the research, said the approach could have major implications for diseases that affect tens of millions of people around the world.

“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 Dr. 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.”

New Therapeutic Possibilities for MND and Other Diseases

The MND Association welcomed the findings and highlighted their potential importance for future treatments.

Chief Scientist at the charity, Dr. Brian Dickie, 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.”