CRISPR Halts Growth of Breast Cancer

Triple-negative breast cancer (TNBC), lacking estrogen, progesterone and HER2 receptors, has the highest mortality rate of all breast cancers. It more frequently strikes women under age 50, African American women, and women carrying a BRCA1 gene mutation. The highly aggressive, frequently metastatic cancer is in urgent need of more effective targeted therapeutics.

A new tumor-targeted CRISPR gene editing system, encapsulated in a nanogel and injected into the body, could offer a genetic treatment, suggest researchers at Boston Children’s Hospital. In a proof-of-principle study, conducted in human tumor cells and live, tumor-bearing mice, the CRISPR system effectively halted the growth of TNBC while sparing normal cells. Peng Guo, PhD,Marsha Moses, PhD and their colleagues have reported the findings in the journal PNAS.

To date, a lack of effective delivery systems has limited the translation of CRISPR gene editing into therapies. One method uses a virus to deliver CRISPR, but the virus cannot carry large payloads and potentially can cause side effects if it “infectscells other than those targeted. Another method packages the CRISPR tools inside a cationic polymer or lipid nanoparticles. But these elements can be toxic to cells, and the body often traps or breaks down the nanoparticles before they reach their destination.

The new approach encapsulates the CRISPR editing system inside a soft “nanolipogel” made up of a nontoxic double layer of fatty molecules and a hydrogel. Antibodies attached to the gel’s surface then guide the CRISPR nanoparticles to the tumor site. (The antibodies are designed to recognize and target ICAM-1, a therapeutic target for TNBC discovered by the Moses Lab in 2014.)

Because the particles are soft and flexible, they can enter cells more efficiently than their stiffer counterparts. Stiffer nanoparticles tend to get trapped by the cell’s ingestion machinery, while the soft particles fused with the tumor cell membrane and delivered their CRISPR payloads directly inside the cell, the researchers found.

Using a soft particle allows us to penetrate the tumor better, without side effects, and with bigger cargo,” says Guo, the study’s first author. “Our system can substantially increase tumor delivery of CRISPR.”


How To End Malaria

Gene-editing technologies that alter mosquitoesDNA could prove critical in the fight against malaria, Bill Gates said on Wednesday, and ethical concerns should not block progress in such gene-modifying research.

Speaking at the Malaria Forum conference in London, the billionaire Microsoft co-founder and philanthropist said that while gene editing raises “legitimate questions”, that should not jeopardize exploration of tools such as CRISPR gene editing and so-called “gene drive” technologies.

I’m very energized about the potential of gene drive. (It’s) the kind of breakthrough we need to support,” Gates said. “It may prove critical here.” 

Gene drive technologies alter DNA and drive self-sustaining genetic changes through multiple generations by overriding normal biological processes. CRISPR technology enables scientists to find and modify or replace virtually any gene. The techniques are being explored across science – from human medicine to livestock– and crop-breeding. In mosquitoes that transmit malaria, genetic alterations can be used to induce infertility to reduce populations, or alter the insects’ ability to carry and pass on the malaria parasite. 

The technologies can be extremely powerful, but they are also controversial, since such genetically engineered organisms released into the environment could have an unknown and irreversible impact on the ecosystem. Asked in a interview with Reuters about that controversy, Gates said there were understandable concerns about safety and efficacy that would need to be addressed in research and trials. But he countered: “Malaria itself is quite controversial – it kills about 400,000 kids a year. So we’re definitely not on the side of malaria.”

He also noted that at their summit in January, leaders of the African Union endorsed gene drive research as part of the fight against a disease that continues to kill their people.