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“Nanospears” for Targeted Delivery of Genes to Patient Cells

UCLA researchers have now developed remote-controlled, needle-like nanospears capable of piercing membrane walls and delivering DNA into selected cells. These magnetically guided nanostructures could enable gene therapies that are safer, faster and more cost-effective.

Researchers, have in the past, used sharp-tipped nanoparticles stuck to surfaces in order to deliver molecules to cells, but removing the altered cells from the nanoparticle-coated surface has been difficult. Other techniques involved self-propelled nanoparticles, but controlling them was not easy. In addition, mobile nanoparticles can generate toxic byproducts.

The UCLA team wanted to make the process more efficient, so they developed biocompatible nanospears that can accurately transport biological material via an external magnetic field. In this way, cells are safe from damage and the use of chemical propellants is no longer necessary.

Just as we hear about Amazon wanting to deliver packages straight to your house with drones, we’re working on a nanoscale equivalent of that to deliver important health care packages straight to your cells,” Dr. Steven Jonas, a clinical fellow in the UCLA Broad Stem Cell Research Center Training Program, said.

Jonas and Paul Weiss, a distinguished professor of chemistry and biochemistry at UCLA, led a research team that designed nanospears that are biodegradable, and can be mass-produced inexpensively and efficiently.

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Nanospear forest: Image shows an array of nanospears before being released for delivery of genetic information to cells. Credit: UCLA Broad Stem Cell Research Center/ACS Nano

The construction of nanospears was inspired by the work of their collaborators, Hsian-Rong Tseng, a professor of molecular and medical pharmacology, and Xiaobin Xu, a postdoctoral fellow in Weiss’ interdisciplinary research group. Tseng and Xu are both co-authors of the study.

Based on Xiaobin’s nanomanufacturing work, we knew how to make nanostructures of different shapes in massive numbers using simple fabrication strategies,” said Weiss, who is also a member of the California NanoSystems Institute. “Once we had that in hand, we realized we could make precise structures that would be of value in gene therapies.

These nanospears, which are made from silicon, nickel and gold, are about 5,000 times smaller than the diameter of a strand of human hair. Yet they include genetic information with minimal impact on cell viability and metabolism. By coating their nanospears with nickel, Weiss and Jonas eliminated the need for chemical propellants. A magnet can be held near a lab dish containing cells to manipulate the direction, position and rotation of one or many nanospears.

Then, researchers tested their invention in a lab dish, where the nanospears had to deliver DNA to brain cancer cells. The cancerous cells were altered so that they would express a green fluorescent protein.

About 80 percent of targeted cells exhibited a bright green glow, and 90 percent of those cells survived. Both numbers are a marked improvement on existing delivery strategies.

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The biggest barrier right now to getting either a gene therapy or an immunotherapy to patients is the processing time,” Jonas said. “New methods to generate these therapies more quickly, effectively and safely are going to accelerate innovation in this research area and bring these therapies to patients sooner, and that’s the goal we all have.

One of the amazing things about working at UCLA is that for each of the targeted diseases, we collaborate with leading clinicians who already have gene therapies in development,” Weiss said. “They have the gene-editing cargo, model cells, animal models and patient cells in place so we are able to optimize our nanosystems on methods that are on the pathway to the clinic.”

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