A new way to deliver mRNA genomes: Nucleocapsids with evolutionary properties
(Phys.org)—A team of researchers at the University of Washington has created microscopic assemblies for packaging genetic material that they call synthetic nucleocapsids. The team hopes the assemblies can one day be used to treat patients with cellular-level problems by delivering appropriate therapies to the cells that could benefit from them. In their paper published in the journal Nature, the team describes their assemblies and what they have done with them thus far.
The development of the assemblies was part of an overall program dedicated to mRNA delivery. mRNA, the team explains, are the molecules that cells use to send messages between DNA (the blueprint) and the proteins that reside in the cells. The idea for the nucleocapsids came from viruses, the group further explains, which encapsulate their payloads as a means of protecting them. In designing their own delivery system, the researchers used proteins to build assemblies containing their own RNA genome. The assemblies can evolve indirectly, the team notes—assemblies are created and then injected into test mice. After a period of time has elapsed, blood is drawn from the test mice and examined to see how well the assembly delivered its load to targeted cells. Changes can then be made to improve desirable characteristics.
The researchers note that the technique allows for large leaps in improvement after just a few iterations. They found, for example, that they could improve the survival rate of an RNA package injected into a mouse after six hours from 3.7 percent to 71 percent. They also found that they could slow circulation time inside of a mouse, from five minutes to four and a half hours, giving an assembly more time to do its job.
The will continue to work with the synthetic nucleocapsids, looking for ways not only to improve performance, but to allow for targeting specific types of cells and carrying a wider range of payloads—including RNA, DNA, and proteins and small-molecule drugs. They are hoping the end product will be a delivery system that can be used to battle cancer, heart disease, and other ailments that involve problems with cells.