Scientists look to gene-inserting tech for T-cell modification

By Flora Southey

- Last updated on GMT

A gene-inserting technology that effectively implants large molecules into cells could help modify T-cells from a patient’s immune system, says researcher.

According to the report published in Nature​, J. Mark Meacham and his team of researchers at Washington University in St. Louis are developing a technology to ‘propel’ complex molecules into cells.

“Delivery of large and structurally complex target molecules [such as DNA, RNA and proteins] into cells is vital to the emerging areas of cellular modification and molecular therapy,” ​said Meacham.

His technique combines Acoustic Shear Poration (ASP) with electrophoresis (EP) to employ ultrasound waves and focused mechanical force to make nanoscale holes in the membrane.

According to Meacham, the holes – or ‘pores’ – are large enough for macromolecules or nanoparticles to access the cell’s interior.

T-cell focus

“We have demonstrated our poration technique using cancer cell lines and patient-derived, primary monocytes, which is an important achievement, but the end goal is to use the new combined method to successfully modify T cells from a patient’s immune system.

“That’s the Holy Grail of personalized medicine and emerging gene therapies,” ​he said.

The researchers are currently focused on demonstrating an ability to scale transfected T-cells to levels required for patients undergoing CAR T therapy.

“The inherent scalability of ASP-EP should accelerate this process,” ​said Meacham.


Due to the difficulty of delivering genes into cells for gene therapies, researchers have been investigating the effectiveness of non-chemical, non-viral approaches, said Meacham.

These approaches – which employ mechanical or electrical stimuli to break through the cell membrane – can be safer, less expensive, and accommodate large-scale manufacturing of therapeutic cells, he added.

According to Meacham, the current system targeting bench-scale science and clinical research is cost-competitive with prevailing electroporation systems, both in terms of fixed and disposable costs.

“Mechano-poration approaches are less sensitive to suspension medium (unlike e.g., electroporation) so reagent costs will be lower.

“We anticipate that scaled-up and GMP [good manufacturing practice] compliant embodiments will also be cost-competitive – or represent a cost saving – with alternative solutions for cell-based therapies based on physical, chemical or viral methods,” ​he added.

Licensing and patents

OpenCell Technologies – of which Meacham is a co-founder – is interested in licensing the development of delivery and transfection applications, including CAR T-cell generation, we were told.

“OpenCell is currently in discussions with potential strategic partners, particularly regarding scale up capabilities geared toward CAR T applications,” ​said Meacham.

The core technology is the subject of seven issued patients – exclusively licensed from Georgia Institute of Technology, where Meacham first worked on the technology – which includes the acoustic shear poration-electrophoresis (ASP-EP) technology, we were told.

Additional applications are underway at OpenCell, Washington University in Saint Louis, and Georgia Tech.

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