A gene called Lipocalin 2 is a major culprit in triple-negative breast cancer, an aggressive form of the disease for which there are few effective, targeted treatments. A team of researchers at Boston Children's Hospital has developed an innovative way to knock out the gene using the editing system CRISPR and has shown its potential for treating triple-negative breast tumors in mice.
But to make CRISPR work in breast tumors, the researchers had to figure out a way to deliver the technology into breast cancer cells without using a virus or something else that might cause off-target side effects. So they encapsulated it in nanoparticles and targeted it at ICAM-1, a molecule expressed on breast cancer cells.
The encapsulated CRISPR system knocked out Lipocalin 2 with 81% efficiency in tumor samples, and when injected into mouse models of triple-negative breast cancer, it slowed tumor growth by 77%. The researchers reported the results in the journal Proceedings of the National Academy of Sciences.
The Boston Children’s team developed flexible particles made of fat and hydrogels. Then they attached antibodies designed to target ICAM-1 to them. The soft nanoparticles entered cells, fused with the cell membrane and then delivered CRISPR inside the cell, they reported.
"Using a soft particle allows us to penetrate the tumor better, without side effects, and with bigger cargo," said co-author Peng Guo, Ph.D., a surgery instructor at Boston Children’s, in a statement. Guo’s team is now discussing the technology with companies that may be interested in developing it, they said.
CRISPR-Cas9 has been hailed as a potential cure for a wide range of diseases driven by faulty genes that are inherited, but several research groups are investigating the technology in cancer, too. Last year, Brigham and Women's Hospital researchers described how they’re using CRISPR to edit cancer cells, turning them into killer cells that could deliver therapies directly to tumors.
Developing safer versions of CRISPR is also a priority in gene-editing research. Earlier this year, a team at the Fred Hutchinson Cancer Research Center said it developed gold nanoparticles that can deliver CRISPR with no toxic side effects. GenEdit, a spinoff from the University of California, Berkeley is also working on a old-based CRISPR system.
The Boston Children’s researchers observed that after they used their nanoparticles to knock out Lipocalin 2 in mice, triple-negative breast tumors became less aggressive and were less likely to metastasize. The mice showed no side effects, they reported. They believe the encapsulated CRISPR technology could prove effective for treating pediatric tumors as well.