Protein fibers, typically associated with Alzheimer's disease, may play a crucial role in sperm: they appear to help transport genetic material into sperm cells. Researchers at the Zuckerman Institute of Columbia University report this finding in the journal "Molecular Cell" (DOI: 10.1016/j.molcel.2026.10.004). In the long term, these proteins, known as amyloids, could contribute to the safer introduction of gene-editing technologies like CRISPR into cells.
“Amyloids are usually considered a hallmark of Alzheimer’s, Parkinson’s, and other neurodegenerative diseases, but they also play functional roles in the rest of the body,” said study leader Anthony Fitzpatrick. The starting point was the observation that amyloid fibrils in sperm can help HIV enter cells of the reproductive tract. Fitzpatrick and first author William Mallen investigated whether the fibrils can also transport the body’s own RNA into sperm – a previously unsolved puzzle.
The researchers showed that amyloids and RNA bind together: amyloids are positively charged, RNA negatively. The fibrils could protect the fragile RNA because they themselves are very durable. Using cryo-electron tomography, the scientists demonstrated that the amyloids actually enter the sperm cells and do not merely adhere to their surface. "Seeing the amyloid fibers inside the sperm cells was extraordinary," said Mallen. Furthermore, amyloids significantly enhance the uptake of RNA; the protein clusterin can then detach the RNA from the amyloid.
In experiments, amyloid fibrils also delivered RNA molecules into sperm cells large enough to code for a green fluorescent protein. Embryos fertilized with these sperm cells produced at least ten times more of this protein than embryos from sperm cells exposed to the RNA without amyloids. This suggests that amyloids could one day deliver therapeutic genes into cells and embryos. CRISPR currently often relies on modified viruses as a delivery mechanism, which can trigger immune responses. "Because the amyloid fibrils we studied are of human origin, there is hope that the immune system will not react in the same way as it does to the repurposed viruses," said Mallen. The function of the amyloid-bound RNA in sperm cells is still unclear; previous studies have shown that RNA in sperm cells can switch genes on or off in offspring.
