Difference between liposomes and lipid nanoparticles (LNPs) as CRISPR delivery

Designing and manufacturing CRISPR gene editing ingredients (e.g., gRNA, Cas9 protein or plasmid DNA) is not complicated now, but before the materials can execute a therapy, they must reach the target site. Typically viral vectors are used to deliver CRISPR agents with high efficiency, they suffer from several drawbacks [1]. Nonviral CRISPR delivery systems have been developing rapidly and shown promise in accommodating large cargos, decreasing immunogenicity and relatively safety.

Liposomes are one of the most widely investigated nonviral carriers for CRISPR/Cas9 delivery.

The word liposome derives from two Greek words: lipo ("fat") and soma ("body"), as its primary composition is phospholipid. Simple liposomes are vesicles that have a shell consisting of a lipid bilayer, which can trap hydrophobic guest molecules within the hydrophobic bilayer, and hydrophilic guests up to several hundred nanometres in its larger interior. [2]

In general, there are four main types of liposomes based on their surface characteristics – conventional liposomes, PEGylated liposomes, ligand-targeted liposomes, and theranostic liposomes (Figure 1. Sercombe et al., 2015).

FIGURE 1. Schematic representation of the different types of liposomal drug delivery systems – (A) Conventional liposome, (B) PEGylated liposome, (C) Ligand-targeted liposome, and (D) Theranostic liposome (Sercombe et al., 2015) [3].

Solid lipid nanoparticles, or lipid nanoparticles (LNPs), are nanoparticles composed of lipids. Their liposome-like structures especially geared towards encapsulating a broad variety of nucleic acids (RNA and DNA) and as such, they are the most popular non-viral gene delivery system. [4]

There are two main differences between liposomes and lipid nanoparticles. 

1. Liposomes are spherical vesicles formed mainly by phospholipids and other physiologic lipids, while lipid nanoparticles are solid particles at room and body temperature, consisting of solid lipids (SLN) or a mixture of a solid lipid and a liquid lipid (NLC).[5]

2. Traditional liposomes include one or more rings of lipid bilayer surrounding an aqueous pocket, but not all LNPs have a contiguous bilayer that would qualify them as lipid vesicles or liposomes. Some LNPs assume a micelle-like structure, encapsulating drug molecules in a non-aqueous core.

(Image credit:  www.exeleadbiopharma.com [4])

How liposomes and LNPs work as CRISPR deliveries

Liposomes are one of the most widely investigated nanocarriers for CRISPR/Cas9 delivery. Cationic formulations dominate CRISPR/Cas9 delivery and neutral formulations also have good performance while anionic formulations are generally not proper for CRISPR/Cas9 delivery. 

Unlike the traditional liposome-based delivery systems, researchers from the University of New South Wales (UNSW) Sydney developed a novel light-triggered liposome CRISPR-Cas9 delivery system, which offers a high degree of spatial and temporal control of gene editing. [6] 

Researchers at Tufts University and the Chinese Academy of Sciences have developed a new lipid nanoparticle which can deliver CRISPR/Cas9 gene editing tools into organs with high efficiency, suggesting that the system is promising for clinical applications.[7]


[1] https://www.genengnews.com/insights/nonviral-crispr-delivery-vehicles-lay-the-smart-siege/

[2] https://www.nature.com/articles/489372b

[3] Sercombe, L., Veerati, T., Moheimani, F., Wu, S. Y., Sood, A. K., and Hua, S. (2015). Advances and challenges of liposome assisted drug delivery. Front. Pharmacol. 6:286. doi: 10.3389/fphar.2015.00286

[4] https://www.exeleadbiopharma.com/news/liposomes-and-lipid-nanoparticles-as-delivery-vehicles-for-personalized-medicine

[5] https://www.sciencedirect.com/science/article/pii/B9780323428682000127

[6] https://pubs.acs.org/doi/10.1021/acsami.0c16380 

[7] https://www.medgadget.com/2019/07/lipid-nanoparticles-deliver-crispr-cas9-into-organs-with-high-efficiency.html

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Nice reading and writing. #Neha Mittal and her team for molecular distinguished award

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