Lipid nanoparticles carry gene-editing cancer drugs past tumor defenses

As they grow, solid tumors surround themselves with a thick, hard-to-penetrate wall of molecular defenses. Getting drugs past that barricade is notoriously difficult. Now, scientists at UT Southwestern have developed nanoparticles that can break down the physical barriers around tumors to reach cancer cells. Once inside, the nanoparticles release their payload: a gene editing system that alters DNA inside the tumor, blocking its growth and activating the immune system.

The new nanoparticles, described in Nature Nanotechnology, effectively stopped the growth and spread of ovarian and liver tumors in mice. The system offers a new path forward for the use of the gene editing tool known as CRISPR-Cas9 in cancer treatment, said study leader Daniel Siegwart, Ph.D., Associate Professor of Biochemistry at UT Southwestern.

“Although CRISPR offers a new approach for treating cancer, the technology has been severely hindered by the low efficiency of delivering payloads into tumors,” said Dr. Siegwart, a member of the Harold C. Simmons Comprehensive Cancer Center.

In recent years, CRISPR-Cas9 technology has given researchers a way to selectively edit the DNA inside living cells. While the gene editing system offers the potential to alter genes that are driving cancer growth, delivering CRISPR-Cas9 to solid tumors has been challenging.

For more than a decade, Dr. Siegwart and his colleagues have been studying and designing lipid nanoparticles (LNPs), small spheres of fatty molecules which can carry molecular cargo (including recent mRNA COVID-19 vaccines) into the human body. In 2020, Dr. Siegwart’s group showed how to direct nanoparticles to specific tissues, which had been a challenge limiting the field.

In the new work, to target cancer, the researchers began with the nanoparticles that they had already optimized to travel to the liver. They added a small piece of RNA (called short interfering RNA or siRNA) that could shut off focal adhesion kinase (FAK), a gene that plays a central role in holding together the physical defenses of a number of tumors.

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