Researchers Uncover How Viruses Pack RNA with Precision

Researchers from San Diego State University and Michigan State University have made significant strides in understanding how viruses efficiently package their genetic material. This research, published in the Proceedings of the National Academy of Sciences on August 15, 2025, may pave the way for advancements in antiviral development and gene therapies.

The study reveals how molecular properties enable viruses to selectively collect their RNA into protein shells known as capsids while disregarding the competing genomes of host cells. These capsids act as protective armor, safeguarding the virus’s genetic material and facilitating its entry into host cells. With some viruses achieving over 99% accuracy in RNA packaging, the implications for synthetic biology are profound.

Kristin Parent, director of Michigan State University’s Cryo-EM Facility and a co-author of the study, emphasized the potential health benefits. “Synthetic capsids can be used to create antivirals that target RNA packaging, impacting human health, agriculture, and veterinary medicine,” she stated.

Collaboration between the Garmann lab at San Diego State University and researchers from Michigan State produced these groundbreaking findings. Rees Garmann, the study’s senior author and an assistant professor at SDSU, noted that some RNA viruses consist of fewer than 200 molecules yet can replicate in vast quantities and form precise nanoscale structures.

The staggering abundance of viruses on Earth is illustrated by Parent’s example: if two handfuls of water are collected from Lake Michigan, they would contain more viruses than there are humans globally. Among these, bacteriophages, which infect and replicate within bacteria, are the most prevalent.

In their research, the team focused on a phage known as MS2, which specifically targets E. coli. When MS2 attaches to a bacterium, it injects its genetic material, compelling the host cell to produce viral copies. The viral coat proteins then assemble around the RNA to create the capsid, which protects the genetic material. The MS2 virus, resembling a soccer ball or a game die, comprises 180 identical coat proteins arranged into 20 faces.

A key question for the researchers was how MS2 efficiently identifies and packages its genome amid the host’s genetic material. Parent explained, “Around 99% of the particles we observe at the end are perfectly formed viral copies, indicating a high-fidelity process.”

To investigate the RNA packaging mechanisms, the researchers systematically altered the MS2 genome, creating RNA constructs with diverse properties like shape, length, and sequence. The results were surprising; the team observed unexpected capsid packaging outcomes, including viral particles that were undersized or had inefficient shapes. Ultimately, they discovered that MS2 coat proteins alone are adept at selectively packaging viral RNA, influenced by various RNA characteristics beyond the previously identified TR stem-loop structure.

Through these findings, the researchers are reshaping our understanding of RNA packaging in viruses. The molecular mechanisms uncovered could be applied to develop synthetic capsids and new genetic cargo, with potential applications in gene editing, vaccines, and the next generation of RNA-based therapeutics.

For more information, refer to the study by Amineh Rastandeh et al, titled “Measuring the selective packaging of RNA molecules by viral coat proteins in cells,” in the Proceedings of the National Academy of Sciences.