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Nucleic acids such as DNA and RNA play a central role in gene therapies and vaccines. They store and transmit biological information. In order for them to work in the body, they must enter the cells using chemical carrier systems. Researchers at the Helmholtz-Zentrum Hereon are now proposing a new strategy for developing such systems: instead of using the same carrier material for different nucleic acids, the carrier should be individually adapted to the respective payload. This could improve the effectiveness of vaccines, for example. The study was conducted in collaboration with the University of Potsdam and Pantherna Therapeutics and has been published in the journal Advanced Science.
DNA and RNA are rapidly broken down in the body and cannot cross cell membranes on their own. They also encounter the immune system in the organism. “Our body's protective mechanisms work against these biologically active substances that we want to deliver specifically to the cell,” explains Dr Hanieh Moradian, a researcher at the Institute for Active Polymers at Hereon's Teltow site near Berlin. “A transport system must be able to overcome these barriers without causing damage.”
Such carrier systems package the nucleic acids, protect them as they travel through the body, and facilitate their entry into the cell. Today, lipid-based nanoparticles dominate clinical use, known from COVID-19 vaccines, for example. They are efficient, but also have disadvantages such as limited stability.
Polymers as an alternative
This is where a new generation of polymer-based carrier systems comes in. “A major advantage of polymers is that they can be chemically modified in a targeted manner,” says Moradian. “This makes it possible to adapt their structure, make them more stable, or modify them so that they remain active in the body for longer.” They could be particularly interesting for applications involving delayed or long-term drug release.
Until now, individual polymer carriers have often been used for multiple nucleic acids.
The researchers are now proposing a new design perspective. It aims to tailor carrier systems specifically to the properties of the payload and thus optimize them for the respective application – from cancer research to vaccines to regenerative medicine. The approach distinguishes between four levels: the chemical structure, size, and mobility of the payload and carrier, their interactions, and the embedding of the carriers in larger structures. The latter has hardly been researched, but could enable controlled, long-term release of nucleic acids.
“Our central message is: you first have to understand what type of nucleic acid you want to transport,” says Moradian. “A large, rigid DNA has different requirements than a short RNA or a medium-length mRNA. If you ignore these differences, you're wasting potential.”
AI as an accelerator
Artificial intelligence could significantly advance the development of polymer-based carriers. The vision: instead of laboriously testing individual materials, robotic systems produce large quantities of different polymers, whose properties can then be systematically compared. “If we understand how certain properties of carriers and payload influence each other, we can feed this information into predictive models,” explains Moradian. “AI-based models could help predict carrier designs that are best suited for a particular payload.”
Cutting-edge research for a changing world
Helmholtz-Zentrum Hereon’s scientific research aims at preserving a world worth living in. To this end, around 1000 employees generate knowledge and research new technologies for greater resilience and sustainability - for the benefit of the climate, the coast and people. The path from idea to innovation leads through a continuous interplay between experimental studies, modeling and AI to digital twins that map the diverse parameters of climate and coast or human biology in the computer. This is an interdisciplinary approach that spans from the fundamental scientific understanding of complex systems to scenarios and practical applications. As an active member of national and international research networks and the Helmholtz Association, Hereon supports politics, business and society in shaping a sustainable future by transferring the expertise it has gained.
Dr Hanieh Moradian
Scientist
Institute of Active Polymers
Tel.: +49 (0)30 450539-504
Mail: hanieh.moradian@hereon.de
https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202512653
Electron microscopy image of a representative polymeric nanoparticle for nucleic acid delivery.
Source: Weiwei Wang
Copyright: Hereon/Weiwei Wang
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Electron microscopy image of a representative polymeric nanoparticle for nucleic acid delivery.
Source: Weiwei Wang
Copyright: Hereon/Weiwei Wang
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