A Better Package for Better Delivery

A team of bioengineers in David Baker’s group have built microscopic assemblies, known as synthetic nucleocapsids, to protect genetic materials they are packaging. These tiny particles encapsulate RNA, allowing it to move around the bodies of mice for hours without being degraded.

The package is like the one from a virus , but it does not naturally get into the cells or replicate themselves. “This allowed us to evolve properties that will be useful for non-viral targeted drug delivery: Improved RNA packaging, lower resistance to blood, and increased circulation time in living mice,” Lajoie and his colleagues said.

David Baker’s group has years of experience in protein design. Instead of directly borrowing the architecture of a naturally occurring virus, the author designed the container from scratch. But they still take advantage from the greatest design tool from nature, evolution, and make it even better. They introduced mutations into the design in order to create different versions of the package, then injected them into mice, harvested them overtime, and finally they were able to pick the best persisted packages.

The authors believe the assemblies could be very useful in targeted drug delivery and other biomedical applications. This research also provided insights into the origin of life. A construct that package their own genetic materials and evolve should be the fundamental function of living things

This cutaway view shows the protein design for a synthetic nucleocapsid known as I53-50-v1. (Nature / UW Graphic / Butterfield, Lajoie et al.)

Credit: Ian Haydon, CC BY-ND

Both of these tiny, soccer ball-like structures package genetic material. On the left, a natural virus. On the right, a computer-generated capsid which cannot replicate. A thousand billion copies of either structure shown above can be packed inside a real soccer ball.

Credit: Kstudio, CC BY

Delivering genetic material is a key challenge in gene therapy.

Reference

• Scientists steal tricks from a virus to build proteins into capsules for drug delivery
• Designer proteins that package genetic material could help deliver gene therapy