DNA taught to thwart membranes
Scientists have worked out how to program DNA robots to poke and prod cell membranes.
Experts say they now know how to best get DNA to communicate with membranes in the human body.
The finding could pave the way for the creation of ‘mini biological computers’ in droplets that have potential uses in biosensing and mRNA vaccines.
UNSW’s Dr Matthew Baker and the University of Sydney’s Dr Shelley Wickham discovered the best way to design and build DNA ‘nanostructures’ to effectively manipulate synthetic liposomes - tiny bubbles which have traditionally been used to deliver drugs for cancer and other diseases.
But by modifying the shape, porosity and reactivity of liposomes, there are far greater applications, such as building small molecular systems that sense their environment and respond to a signal to release a cargo, such as a drug molecule when it nears its target.
Dr Baker says the study discovered how to build “little blocks” out of DNA and worked out how best to label these blocks with cholesterol to get them to stick to lipids, the main constituents of plant and animal cells.
“One major application of our study is biosensing: you could stick some droplets in a person or patient, as it moves through the body it records local environment, processes this and delivers a result so you can 'read out', the local environment,” Dr Baker says.
Liposome nanotechnology has shot into prominence with the use of liposomes alongside RNA vaccines such as the Pfizer and Moderna COVID-19 vaccines.
“This work shows new ways to corral liposomes into place and then pop them open at just the right time,” Dr Baker says.
“What's better is because they are built from the bottom-up out of individual parts we design, we can easily bolt in and out different components to change the way they work.”
Previously, scientists have struggled to find the right buffer conditions for lipids and liposomes to make sure that their DNA ‘computers’ actually stuck to liposomes.
They also struggled with the best way to decorate the DNA with cholesterols so that it would not only go to the membrane but stay there as long as was needed.
“Is it better at the edge? The centre? Heaps of them? Few of them? Close as possible to structure, or far as possible?,” Dr Baker says.
“We looked at all these things and showed that we could make good conditions for DNA structures to bind to liposomes reliably and 'do something'.”
Dr Baker says membranes are critical in life as they allow compartments to form and therefore different types of tissue and cells to be separated.
“This all relies on membranes being generally quite impermeable,” he says.
“Here we have built totally new DNA nanotechnology where we can punch holes in membranes, on demand, to be able to pass important signals across a membrane.”