Integrating Cleavage, Deprotection, and TFF: How Asahi Kasei’s THESYS® Platform Is Reshaping Oligonucleotide Manufacturing

As demand for DNA and RNA therapeutics continues to accelerate, manufacturers are under increasing pressure to improve efficiency, reduce risk, and scale production without expanding facility footprints. One emerging solution is the integration of traditionally separate downstream steps into a single automated platform.

Asahi Kasei Bioprocess, has addressed this need with the THESYS® platform, a suite of oligonucleotide manufacturing technologies designed to streamline workflows from synthesis through downstream processing.

In a recent podcast, Sagar Bhatt, Senior Project Engineer at Asahi Kasei Bioprocess America, discussed the development of an integrated system within the THESYS C&D/TFF system combines cleavage, deprotection (C&D), and tangential flow filtration (TFF), and why this shift represents a meaningful evolution in oligonucleotide manufacturing.

Rethinking a Fragmented Workflow

Historically, oligonucleotide production has relied on a series of disconnected unit operations. Cleavage, deprotection, ultrafiltration, and diafiltration are often performed across multiple systems, sometimes even in different rooms.

“Cleavage and deprotection are often carried out using fairly basic setups… and in many cases, they still involve a lot of manual handling,” Sagar explained. “They also typically require additional equipment, like separate tanks, which adds complexity to the process.”

This fragmented approach introduces several challenges. Material transfers between systems increase processing time and create opportunities for product loss. In addition, deprotection reactions, particularly for RNA, require careful thermal control due to heat generated during acid addition.

“If the rate of the acid addition and resulting temperature rise are not controlled carefully, it can negatively impact the product… and damage product quality.”

Facility constraints add another layer of complexity. Because oligonucleotide processing often involves flammable solvents, operations must occur in hazardous environments. However, traditional filtration systems are not typically designed for these conditions, forcing manufacturers to physically move material between areas.

Recognizing these inefficiencies, Sagar and his team saw an opportunity to simplify.

“By integrating these operations into a single physical equipment and related automation, we could potentially streamline the workflow, reduce handling steps, and significantly improve overall manuf