March 08, 2017

Automating gene therapy - moving from factories to appliance scale gene therapy machines and then to picofluidic chips

In October, Adair demonstrated a new technology she thinks could democratize access to gene therapy. Tweaking a cell-processing device sold by German instrument maker Miltenyi, she mostly automated the process of preparing blood cells with a gene therapy for HIV that her center is also testing. Cells dripped in one end came out the other 30 hours later with little oversight needed. She even added wheels. Adair calls the mobile lab “gene therapy in a box.”

Adair thinks a key job for the mobile gene-therapy lab is to extend experimental studies to the developing world, including Africa, where most HIV cases are. “We wanted to show that we could make the trial mobile, because we are kidding ourselves that treating someone in Seattle is going to have the same risks and outcomes as in South Africa,” she says.

Gene therapy is moving quickly from experiment to medical reality. But with potential treatments for cancer and rare diseases now showing promise, scientists are worried that the technology is so complex that patients will not benefit as quickly as they should because of a shortage of trained technicians and suitable facilities. For the most successful gene therapies, those that require modifying blood cells outside the body, the procedures are offered only by a dozen or so research centers, all in major cities like New York, Seattle, Milan, and Paris.

Cancer treatment

Helping to drive interest in portable gene-therapy devices is a new form of cancer therapy, known as CAR-T, that reprograms the DNA of immune system sentinels called T cells so they attack tumors. A growing pack of biotech companies has raised billions of dollars to test these treatments, which also require taking a person’s blood and performing the gene addition in a specialized facility.

One of the first CAR-T treatments to reach the marketplace will probably come from Novartis. The Swiss drug giant last year completed a global test of children with leukemia in which 82 percent of the kids saw their tumors evaporate, and many stayed cancer-free.

Novartis will apply for permission to sell the treatment this year, but the company isn’t too happy with how the therapy is made. For its study, Novartis says that it air-shipped patients’ cells back and forth to a single cell-processing factory it owns in Morris Plains, New Jersey, with the help of Cryoport, a company specializing in shipping frozen cells. It’s logistically complex, labor-intensive, expensive, and potentially unpredictable, since no two people’s cells are the same. What’s more, Novartis isn’t certain how many patients it will actually be able to treat.

“We are limited in the number of patients we can treat given the cumbersome supply chain that we have going,” says Philip Gotwals, chief of exploratory immune-oncology at Novartis. “If we don’t do anything to automate the process, you would have to [build more of] these large factories, and I don’t know if the industry would do that.”

Less elite

Miltenyi, the German device maker, says its instrument, called Prodigy, can already largely automate CAR-T production, and is now being tested by a few companies. The instrument, which weighs about 150 pounds, looks a little like a machine from Willy Wonka’s factory, with bright pastel casements, neatly placed dials, and twists and turns of disposable tubing covering its surface. Instead of hot chocolate, a patient’s cells move through the tubes, mixing with chemicals that stimulate them and, eventually, a load of DNA-carrying viruses used to alter their genetic code.

The instrument costs about $150,000, and a kit of supplies to process one patient’s cells costs another $12,000. Katharina Winnemöller, a marketing manager based in Germany, says doctors in London will use the box to treat cancer patients with CAR-T cells in coming months.

Novartis’s Gotwals says Miltenyi’s gadget is just one of several devices under development. Last summer, after predicting CAR-T cancer treatments could generate $10 billion in sales by 2021, General Electric acquired a company called Biosafe that specializes in cell handling. MIT’s Draper Laboratories is working on microfluidics devices to prepare CAR-T treatments, and a California startup, Berkeley Lights, has new ways to sort through blood cells to zero in on just the right ones.


Berkeley Lights delivers a fundamentally new approach to biopharmaceuticals, genomics and clinical applications. Through simultaneous manipulation, analysis and selection of single cells, BLI develops highly sensitive, massively parallel, integrated workflows with single cell resolution. Initial applications of BLI’s technology are in biologic discovery and development as well as single cell annotation and genomics.

Manipulate Cells with Light

BLI’s breakthrough technologies enable interactive biology at the cellular level using automated biosystems, integrated nanofluidic chips and OptoSelect™ visible light technology. OptoSelect™ technology represents a new approach to cellular and molecular biology that uses low-intensity visible light to precisely manipulate cells, beads and reagents. OptoSelect™ has two modes: OptoElectroPositioning (OEP) and OptoElectroWetting (OEW).

OptoElectroPositioning – OEP

BLI lets biologists directly view and manipulate individual cells (or other micro-objects) using OptoSelect™ OEP. Cells can be manually or automatically selected based on cell surface markers, morphology and real-time protein secretion levels.

OptoElectroWetting – OEW

OptoSelect™ OEW technology uses light to manipulate aqueous droplets, allowing biologists to aliquot, measure, titrate, combine, split and dilute at nanoliter volumes. When combined with our OEP technology, these capabilities allow the true miniaturization of laboratory processes onto a single computer-controlled chip.

BLI Nanofluidic Biosystems

Most laboratory equipment work at ~50 microliter fluidic volumes, whereas a single cell has a volume of ~1/2 picoliter — a hundred million fold difference! Capabilities performed today at microliter scale are now integrated by BLI onto single nanofluidic chips at volumes properly scaled to your cells.

Interactive Cellular Biology… Finally

BLI enables biologists to finally perform cellular biology and choose each cell for experimentation with complete control, full annotation and a complete videographic record. By streamlining and integrating existing workflows with single-cell resolution, and enabling new workflows, BLI has multiple research and commercial partnerships now deploying its technology.




SOURCES MIT Technology Review, Berkeley Lights


Форма для связи

Name

Email *

Message *