Karolinska Institutet’s breakthrough in extracellular vesicle engineering promises targeted delivery of advanced therapeutics, potentially transforming treatments for genetic and neurological disorders.
Key Points at a Glance
- Engineered extracellular vesicles (EVs) enhance delivery of therapeutic proteins and RNA into cells.
- Integration of viral fusogenic proteins and bacterial inteins improves cellular uptake and cargo release.
- Successful delivery of gene-editing tools observed in mouse brain studies.
- Potential applications include treatment of systemic inflammation and central nervous system diseases.
In a significant advancement for targeted medicine, researchers at Karolinska Institutet have developed a novel technique that enhances the delivery of therapeutic proteins and RNA into cells. This method, detailed in Nature Communications, utilizes engineered extracellular vesicles (EVs) to efficiently transport and release therapeutic agents within target cells.
Extracellular vesicles are nanoscale, membrane-bound particles naturally secreted by cells, capable of transferring biologically active molecules between cells. The research team improved these vesicles by incorporating two critical components: a segment of a bacterial protein known as intein and a fusogenic protein derived from a virus.
The fusogenic protein facilitates the fusion of EVs with the endosomal membrane of target cells, promoting the release of their contents into the cytoplasm. Concurrently, the intein component enables the precise release of therapeutic proteins within the cell by self-cleaving.
“This innovative engineering strategy represents a major step forward for extracellular vesicle technology, effectively overcoming key barriers such as poor endosomal escape and limited intracellular release,” stated Professor Samir EL Andaloussi, the study’s senior author.
In vivo experiments demonstrated the efficacy of these engineered EVs in delivering gene-editing tools. When loaded with Cre recombinase and introduced into mouse brains, significant cellular changes were observed in the hippocampus and cortex regions. This suggests potential applications in treating central nervous system disorders like Huntington’s disease and spinal muscular atrophy.
Additionally, the technique showed promise in addressing systemic inflammation in animal models, indicating a broader therapeutic potential.
Dr. Xiuming Liang, the study’s first author, emphasized the broader implications: “By improving the efficiency and reliability of therapeutic delivery into target cells, this technology could significantly broaden the application of advanced medicines.”
This research was conducted within the Karolinska ATMP Center, underscoring the institute’s commitment to advancing cell and gene therapies.
Source: Karolinska Institutet
