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Gene Therapy Company Exploring DNA Circuit Technology

Circuit graphic

(Gerd Altmann, Pixabay)

13 Apr. 2021. Spark Therapeutics, a developer of gene therapies, is gaining access to a technology that programs DNA sequences like integrated electronic circuits. The agreement with Spark Therapeutics in Philadelphia could bring Senti Biosciences in South San Francisco, California more than $645 million if all terms of the deal are fulfilled.

Spark Therapeutics, a subsidiary of global drug maker Roche, is a pioneer in developing therapies addressing inherited diseases. The company is collaborating with Senti Biosciences on designing more precisely targeted gene therapies against unspecified cell targets in the central nervous system, eyes, and liver. With that partnership, Spark gains an option to license Senti Bio’s DNA circuit technology for those applications.

Up to now, Senti Bio designed therapies with computer-like logic from synthetic genes programmed to operate like software in engineered immune system cells. The company’s DNA circuit therapies allow for cells to be programmed with instructions from synthetic genes, providing more control over delivery of therapies to address varying levels of severity, and even multiple illnesses at once.

Moreover, says the company, DNA circuits can be designed, built, and tested with much the same iterative development approach as integrated circuits. And, says Senti Bio, DNA circuits can act as “smart sensors” for disease indicators to deliver treatments to precise locations in the body, and build in safeguards against adverse effects.

Smart sensors are designed to contain DNA circuits called synthetic promoters that precisely control expression of therapeutic genes. “We view gene circuits,” says Senti Bio CEO Tim Lu in a company statement, “as a critical component of any advanced cell and gene therapy, regardless of therapeutic area or delivery modality.”

Option to license synthetic promoter DNA circuits

Spark Therapeutics plans to adapt Senti Bio’s technology, including smart sensors, for gene therapies that deliver treatments to specific types of cells or meeting precise therapeutic conditions. The agreement calls for Senti Bio to design, build, and test synthetic promoter DNA circuits for gene therapies targeting specified, but undisclosed, central nervous system, eye, and liver disorders.

“We look forward to leveraging Senti Bio’s high-throughput synthetic promoter capabilities,” says Spark’s chief scientist Federico Mingozzi in a company statement, “to develop novel gene therapies directed toward specific cell types in the central nervous system, eye or liver.”

The deal gives Spark Therapeutics an option to exclusively license synthetic promoter circuits developed under the agreement. Should Spark go ahead with licensing, the company will be responsible for further preclinical and clinical development, as well as commercialization of gene therapies using Senti Bio’s synthetic promoters.

Spark is paying Senti Bio an unspecified initial fee, and funding its research under the agreement. In addition, Senti Bio is eligible for payments once the option is exercised, and for achieving specified development, regulatory, and sales milestones, as well as royalties on sales. Total value of these payments may exceed $645 million.

Senti Bio is a three year-old company, founded by researchers in biology and engineering at Harvard University, Boston University, and MIT. Science & Enterprise reported on the company’s start-up in February 2018 and second venture funding round in January 2021.

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