Columbia Researchers Discover How Amyloid Fibres Help Carry RNA Into Sperm and Embryos

Researchers at Columbia University have uncovered a previously underappreciated role for amyloid fibres in semen, showing how these protein structures can help transport RNA into sperm cells and deliver it to early embryos. The findings offer new insight into reproductive biology and suggest a possible direction for future RNA-delivery technologies, although the work is still at the experimental stage.

The study, led by William S. Mallen and senior author Anthony W.P. Fitzpatrick at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute, was published in Molecular Cell on October 26, 2026. It examines how extracellular RNA in seminal fluid can associate with protein fibres, enter sperm and reach an embryo following fertilisation.

What are amyloid fibres, and why are they important?

Amyloids are organised protein assemblies often discussed in connection with neurodegenerative diseases, including Alzheimer’s and Parkinson’s. However, not all amyloids are harmful. Some occur naturally and perform biological functions.

The Columbia team investigated amyloid-forming peptides found in seminal fluid, focusing on fragments of prostatic acid phosphatase, or PAP. These peptides carry a positive electrical charge, while RNA has a negatively charged backbone. The researchers found that the two can associate and form concentrated molecular droplets that mature into amyloid fibrils.

This interaction may help protect fragile RNA molecules from degradation and provide a structure that can transport them. The work therefore adds a potential beneficial role to the growing understanding of functional amyloids in the human body.

How the researchers tracked RNA into sperm

To investigate the process, the researchers combined biochemical experiments, fluorescence-based measurements, protein analysis and advanced electron microscopy.

Cryo-electron tomography, or cryo-ET, allowed the team to examine frozen biological samples in three dimensions. By attaching gold nanoparticles to amyloid fibrils, researchers could distinguish the labelled structures from surrounding material and identify fibrils inside sperm cells rather than merely attached to their surfaces.

The imaging work included bovine sperm, while separate experiments assessed uptake in human sperm. The researchers also examined amyloid-containing material isolated from human seminal fluid, strengthening the connection between the laboratory mechanism and naturally occurring reproductive biology.

The results supported the idea that amyloid fibrils can enter sperm and act as carriers for RNA. The process is important because sperm can acquire RNA molecules from their surrounding environment, but how some extracellular RNA reaches the sperm interior has remained an open research question.

Clusterin may help release the RNA cargo

Transporting RNA is only part of the process. For the RNA to have an effect, it must also become available after delivery.

The researchers investigated clusterin, a protein associated with amyloid regulation. In laboratory assays, clusterin helped separate RNA from PAP amyloid fibrils. This suggests that the amyloid structure can function as a carrier while other proteins help release its cargo.

The precise sequence of events inside sperm and embryos still needs further investigation. Nevertheless, the findings point to a potentially regulated system rather than an entirely passive interaction between protein fibres and RNA.

Embryos produced more than ten times the reporter protein

One of the study’s most notable results came from in-vitro fertilisation experiments using mouse sperm and mouse embryos.

Researchers exposed sperm to messenger RNA, or mRNA, encoding enhanced green fluorescent protein (EGFP). This reporter protein is commonly used in laboratory studies because its production can be measured. The team compared embryos resulting from sperm exposed to the RNA with and without PAP amyloid fibrils.

The resulting two-cell-stage embryos showed at least an order-of-magnitude increase in EGFP protein when the fibrils were present. In other words, the measured reporter-protein level was at least ten times higher than in the comparison group.

This result supports the conclusion that amyloid-assisted RNA delivery can produce a functional outcome: the transferred mRNA was available for translation into protein. It does not mean that every type of RNA will be delivered with the same efficiency, or that the study demonstrated a tenfold increase in normal embryo development, fertility or live births.

The team also used labelled RNA experiments to investigate whether RNA could reach embryos following fertilisation. Together, these findings provide experimental evidence for a pathway connecting seminal-fluid amyloids, sperm and the early embryo.

What the discovery means for paternal epigenetic inheritance

Paternal epigenetic inheritance concerns how information beyond changes to DNA sequence may influence gene activity in offspring. RNA carried by sperm has been investigated as one possible contributor to these effects, including in animal studies linking parental environmental exposures with changes in offspring biology.

The Columbia study offers a possible explanation for how some RNA molecules in seminal fluid could be transported into sperm. However, the researchers have not established what all of the naturally carried RNA molecules do after entering sperm, nor whether this particular mechanism accounts for specific inherited traits in humans.

The discovery therefore helps address a mechanistic question without resolving the broader debate about the extent and importance of paternal epigenetic inheritance in human health.

Could amyloid fibres become a new gene-delivery technology?

The research also raises a potential biotechnology application. RNA-based treatments and gene-editing systems need effective ways to deliver their molecular components into cells. Researchers currently use several approaches, including lipid nanoparticles and viral vectors, each with different benefits and limitations.

Because the studied amyloid-forming peptides are derived from human biological material, scientists may investigate whether engineered versions could provide a useful alternative or complement to existing delivery systems. The experiments demonstrate a promising biological mechanism, not a ready-to-use therapeutic platform.

Important questions remain about safety, immune responses, consistency, cargo capacity, targeting and whether the approach can work in cell types beyond sperm. The study does not establish that these fibrils are non-immunogenic, that they can safely deliver CRISPR components in patients, or that they are superior to existing technologies.

The work also does not justify introducing experimental amyloid-based methods into fertility treatment. Any potential use in assisted reproductive technology would require extensive independent research, safety testing and appropriate regulatory review.

What happens next?

The next steps for this field include clarifying how amyloid-RNA complexes enter sperm, determining how the RNA behaves after fertilisation, and testing whether the mechanism can be adapted safely for controlled delivery applications.

For now, the principal achievement is a clearer understanding of how a naturally occurring protein structure may help move RNA from seminal fluid into sperm and early embryos. The findings open a new research direction at the intersection of reproductive biology, epigenetics and molecular delivery systems, while leaving its clinical and commercial potential to be established by future studies.