Super-porous material transports cancer-killing CRISPR inside cells
The CRISPR/Cas9 gene-editing tool has shown promise in treating a wide range of diseases, but getting it into cells in the first place can be challenging. Now, researchers in Australia have packaged the tool inside porous materials called metal organic frameworks (MOFs) coated in a green tea compound, and used it to silence key genes in prostate cancer cells.
Since viruses can naturally enter host cells, they’re often hijacked and made to carry medical payloads into specific cell types to do their work. For CRISPR, an inactivated virus called adeno-associated virus (AAV) is the most common vehicle, already in use in several trials. But AAV has its issues – it can trigger harmful immune responses, and because it’s such a common virus many patients already have some immunity to it, preventing it from reaching the target.
Non-viral delivery systems could be a safer alternative, plus they can be designed to carry bigger payloads and are simpler and cheaper to manufacture in large amounts. For the new study, researchers at RMIT University and CSIRO examined how well MOFs could work in carrying CRISPR into cancer cells.
MOFs are materials with extremely high surface areas for their size – theoretically, just one teaspoon of the stuff has the same surface area as a football field. That makes them great for trapping molecules, and in recent years MOFs have been used as efficient desalination filters, or capturing certain molecules from the air, such as carbon dioxide or drinkable water.
Drug delivery is another avenue in which MOFs have potential, with previous studies showing that they can help ibuprofen relieve pain faster and last longer. For the new study, the team loaded MOFs with a plasmid form of CRISPR/Cas9, and introduced them to prostate cancer cells in culture.
Rather than cutting DNA, this variation of CRISPR was designed to silence the RPSA gene, which codes for a protein called LAM67R. Overexpression of this protein has been linked to cancer spreading and developing new blood vessels to sustain its cells better, while silencing it has been shown to induce cell death.
The team found that the CRISPR-carrying MOF was able to enter the prostate cancer cells effectively, and start killing them. The cells’ viability dropped from 72 percent at 24 hours after the treatment, down to just 34 percent by the 96-hour mark. Interestingly, the method worked even more effectively when it was coated in EGCG, a chemical found in green tea.
“We found an increase in cellular uptake of more than 23 percent for EGCG coated MOFs compared to uncoated ones,” says Arpita Poddar, co-author of the study.
It’s still very early days for this research. The technique has so far only been tested in cell cultures, so there’s no guarantee it would work in animals, let alone humans. Further work will need to be done, and the team also plans to investigate how the method could target other diseases.
The research was published in the journal ChemComm.