Safer, targeted method to deliver CRISPR genome therapy developed

Light-activated liposomes may deliver CRISPR gene therapy more safely than current methods, researchers have found.

Liposomes are spherical fat structures which resemble cell membranes and can be used to encapsulate and deliver drugs or genes to patients' cells. For the first time, researchers from the University of New South Wales (UNSW) in Sydney, Australia, have used liposomes to transport CRISPR/Cas9 molecules. They discovered that light could activate the liposomes to deliver CRISPR gene therapy to specific target sites.

'Unlike the traditional liposome-based delivery systems, our liposomes can be "turned on" under light illumination,' explained lead author Dr Wei Deng, of UNSW. 'When light is shone onto the liposomes, they can be disrupted at once, immediately releasing the entire payload.'

The study, reported in ACS Applied Materials and Interfaces, investigated liposomes as a CRISPR delivery system in human cells in vitro and in a zebrafish animal model. CRISPR/Cas9 is able to cut damaged regions of the genome, and replace these with new, specified sequences. Currently, benign viruses are used to inject CRISPR components into target cells. However, side effects can include unpredictable genome targeting, and immune reactions to the virus.  

Dr Deng and her team found that using liposomes rather than viruses, they could better control the time and location of CRISPR/Cas9 genome editing. They used LED light to break down liposomes once they had entered cells, causing them to release their contents. The method was effective at depths up to one centimetre below the skin of the animal model. Although previous research has demonstrated light-induced liposome degradation, this is the first time it has been achieved in the context of CRISPR delivery.

The team at UNSW hope to build on their findings by increasing the depth at which they can activate the liposomes. Previous work by Dr Deng and colleagues, published in Nature Communications in 2018, showed that X-rays could also stimulate liposomes to unload their cargo. As X-rays are able to penetrate further into the body than visible light, this could make liposome delivery a new option for treating diseases such as cancer.

'We fully expect that we will be able to carry out X-ray triggering of CRISPR delivery in deep tissue at depths greater than one centimetre,' said Dr Deng.

The technique could further improve the precision of the already revolutionary CRISPR/Cas9 approach – which earnt Professors Jennifer Doudna and Emmanuelle Charpentier the Nobel Prize in Chemistry earlier this year (see BioNews 1067).

Dr Deng summarised: 'CRISPR technology has created a very promising tool for developing new targeted, gene and cell-based therapies. Its outcomes would largely increase with the desired delivery system, and in this context, our findings may provide such a system.'