Targeted delivery of RNA using synthetic bacterial spores

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Biology

Background:

• RNA therapy shows promise but faces challenges in targeted delivery and RNA loading efficiency.
• Synthetic bacterial spore-like particles (SSHELs) offer a biocompatible platform for drug delivery.
• Previous work established SSHELs with a silica core, lipid bilayer, and modifiable protein surface.

Purpose of the Study:

• To develop SSHELs for targeted delivery of mRNA and siRNA to specific cancer cells.
• To enhance RNA loading efficiency and cargo capacity using SSHELs.
• To evaluate the efficacy of SSHELs in delivering RNA to HER2-positive cancer cells.

Main Methods:

• Micron-scale SSHELs were constructed using a fusogenic lipid.
• SSHELs were decorated with affibodies targeting the HER2 receptor.
• Model mRNA and siRNA molecules were loaded into SSHELs for delivery studies.

Main Results:

• SSHELs demonstrated specific delivery of RNA to HER2-positive ovarian and breast cancer cells.
• High RNA loading efficiency and cargo capacity were achieved with the SSHEL system.
• The modified SSHELs successfully delivered therapeutic RNA payloads to target cells.

Conclusions:

• SSHELs are a versatile and effective vehicle for targeted RNA delivery.
• This platform addresses key limitations in current RNA-based therapeutic strategies.
• SSHELs show potential for treating various diseases by enabling precise delivery of RNA therapeutics.