Bio-Inspired Liquid Compartments for Efficient Encapsulation and Controlled Release of Payloads

Tunable peptide-RNA microcompartments inspired by viral structures that have high encapsulation efficiency of small organic molecules and large macromolecules that their release is triggered by light.  

Current drug delivery or microreactor systems are lipid-based nanoparticles (NPs) that has shown a wide range of applications as drug delivery vehicles and are used for various treatments including cancer, central nervous system diseases, microbial infections and more. As these structures are strongly hydrophobic, therefore not water-soluble, they require energy-consuming homogenization processes so those particles would be extremely small (nano-scale) and with a high specific surface area that allows water solubility. 

We developed synthetic compartments that are formed by liquid-liquid phase separation (LLPS) of minimalistic designed peptide building blocks and RNA. These liquid compartments have several advantages as an encapsulation and delivery platform:
• High permeability – Open compartments that easily encapsulate and release various payloads without any need of active transport.
• Efficient encapsulation that can get to the milli-scale and loading capacity of various organic molecules and large biomolecules. Lipid NPs encapsulate in the nano-scale. 
• Spontaneous assembly in physiological conditions and buffers. 
• Versatility – The peptide building block can be tuned in the single amino acid level to achieve specific compartment properties for encapsulation of specific molecules such as small-molecule hydrophobic drugs, large enzymes/proteins, and highly polar polymers such as RNA/DNA/peptides.
• Spatiotemporal controlled release – Incorporating a side-chain photocleavable group to the peptide sequence allows light-controlled release of payload at a specific location and time. 

• Spontaneous encapsulation of various molecules. 
• Solubilization of hydrophobic molecules that sediment/aggregate in physiological conditions. 
• Segregation of unwanted reaction products – Compartments can be tuned to encapsulate these.
• On-demand release of payload through light spatiotemporal control.  

• Compartments are proved to encapsulate and release several molecules including – RNA, DNA, enzymes, nucleotides, small organic molecules. 
• We showed that tuning the peptide sequence at a single amino acid level allows to regulate compartments’ materials properties and encapsulation of various molecules. 

Figure 1. Design of viral factory-inspired liquid compartments. a. Schematics of the measles virus viral factories. b. Design of viral factory inspired peptide (VFP-1, inspired by measles protein) c. Liquid compartments formed by LLPS of a photo-protected peptide and RNA. Release of specific payload (red) from the compartments can be regulated by UV light. 

US Provisional Patent.

1. Katzir, I., Haimov, E., & Lampel, A. (2022). Tuning the Dynamics of Viral Factories‐Inspired Compartments Formed by Peptide‐RNA Liquid‐Liquid Phase Separation. Advanced Materials, 2206371. https://doi.org/10.1002/adma.2…

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