Researchers at Karolinska Institutet have developed a way that allows environment friendly supply of therapeutic proteins and RNA to cells. The tactic, revealed in Nature Communications, exhibits promising leads to animal research to ship gene editors and protein therapeutics.
The tactic is predicated on so-called extracellular vesicles (EVs), tiny bubbles which might be naturally secreted by cells and may transport biologically energetic molecules between cells. Researchers have now succeeded in enhancing these bubbles by introducing two key parts: a small a part of a bacterial protein referred to as intein and a so-called fusogenic protein from a virus.
The fusogenic protein helps the bubbles to fuse with the endosomal membrane and launch their contents into the cell, whereas the intein can minimize itself and thus assist launch therapeutic proteins contained in the cell.
“This progressive engineering technique represents a significant step ahead for extracellular vesicle expertise, successfully overcoming key obstacles resembling poor endosomal escape and restricted intracellular launch,” says Professor Samir EL Andaloussi, final writer of the examine and researcher on the Division of Laboratory Drugs.
“Our in vivo findings spotlight the potential of engineered EVs as a flexible platform for delivering therapeutics to deal with a broad vary of situations, together with systemic irritation, genetic ailments, and neurological problems.”
The examine’s first writer, Dr. Xiuming Liang on the Division of Laboratory Drugs, provides, “By enhancing the effectivity and reliability of therapeutic supply into goal cells, this expertise may considerably broaden the applying of superior medicines.”
Mind adjustments in mice
In experiments on cells and dwell animals, the researchers had been capable of effectively ship Cre recombinase, a protein that may minimize and paste DNA, and Cas9/sgRNA complexes, that are used to edit genes. When extracellular vesicles loaded with Cre recombinase had been injected into the brains of mice, a big change in cells within the hippocampus and cortex mind constructions was noticed.
“This offers hope to make use of the CRISPR/Cas9 gene scissors or comparable instruments to deal with extreme genetic ailments of the central nervous system, resembling Huntington’s illness and spinal muscular atrophy,” says Liang.
The researchers additionally demonstrated that the approach may very well be used to deal with systemic irritation in mice.
Extra info: Xiuming Liang et al, Engineering of extracellular vesicles for environment friendly intracellular supply of multimodal therapeutics together with genome editors, Nature Communications (2025). DOI: 10.1038/s41467-025-59377-y. www.nature.com/articles/s41467-025-59377-y