What are the key takeaways from this Beyond Biotech episode?

Key insights include: **Circular RNA stability advantage:** Circular RNA uses natural nucleotides rather than chemical modifications like pseudouridine or 5-prime caps, allowing it to evade innate immune sensors naturally. This produces a longer half-life than linear mRNA in vivo, extending the therapeutic window and enabling sustained protein expression — a structural property that makes redosing feasible without reformulation.; **Scarless ligation manufacturing method:** Therona's splint-free enzymatic ligation method splits the IRES sequence and places fragments on both sides of the coding region, allowing the linear precursor to self-fold and ligate under mild conditions. This eliminates splicing byproducts that require purification, reduces manufacturing complexity, and has already been validated under GMP for three clinical-stage products.; **In vivo CAR-T without lymphodepletion:** TI-0032 delivers circular RNA via antibody-coated lipid nanoparticles that target T cells directly in the body. In nonhuman primates, the approach achieved complete B-cell depletion at low dose levels. Unlike autologous CAR-T, it requires no cell extraction, no lymphodepletion, and can be manufactured as an off-the-shelf product at a fraction of the cost.

What did Lu Gao discuss on Beyond Biotech?

Beijing-based Therona Inc., founded in 2021, has built a circular RNA platform with three active clinical programs — prophylactic vaccine, therapeutic cancer vaccine, and in vivo CAR-T — while remaining largely unknown to Western pharma. CEO Lu Gao outlines the science, manufacturing approach, and dual US-China IND strategy for lead asset TI-0032. Key topics include: **Circular RNA stability advantage:** Circular RNA uses natural nucleotides rather than chemical modifications like pseudouridine or 5-prime caps, allowing it to evade innate immune sensors naturally. This produces a longer half-life than linear mRNA in vivo, extending the therapeutic window and enabling sustained protein expression — a structural property that makes redosing feasible without reformulation.; **Scarless ligation manufacturing method:** Therona's splint-free enzymatic ligation method splits the IRES sequence and places fragments on both sides of the coding region, allowing the linear precursor to self-fold and ligate under mild conditions. This eliminates splicing byproducts that require purification, reduces manufacturing complexity, and has already been validated under GMP for three clinical-stage products..

How long is this episode of Beyond Biotech?

This episode is 36 minutes long. SignalCast provides an AI-generated summary so you can get the key insights in about 3 minutes.

Beyond Biotech

Why Western pharma is sleeping on China's circular RNA revolution

August 7, 2026

36 min episode · 2 min read

Lu Gao

Episode

36 min

Read time

2 min

Topics

Health & Wellness, Relationships, Fundraising & VC

AI-Generated Summary

Published Aug 7, 2026

Key Takeaways

✓Circular RNA stability advantage: Circular RNA uses natural nucleotides rather than chemical modifications like pseudouridine or 5-prime caps, allowing it to evade innate immune sensors naturally. This produces a longer half-life than linear mRNA in vivo, extending the therapeutic window and enabling sustained protein expression — a structural property that makes redosing feasible without reformulation.
✓Scarless ligation manufacturing method: Therona's splint-free enzymatic ligation method splits the IRES sequence and places fragments on both sides of the coding region, allowing the linear precursor to self-fold and ligate under mild conditions. This eliminates splicing byproducts that require purification, reduces manufacturing complexity, and has already been validated under GMP for three clinical-stage products.
✓In vivo CAR-T without lymphodepletion: TI-0032 delivers circular RNA via antibody-coated lipid nanoparticles that target T cells directly in the body. In nonhuman primates, the approach achieved complete B-cell depletion at low dose levels. Unlike autologous CAR-T, it requires no cell extraction, no lymphodepletion, and can be manufactured as an off-the-shelf product at a fraction of the cost.
✓Autoimmune disease as primary CAR-T target: Therona prioritizes autoimmune indications over oncology for TI-0032 because B-cell-driven autoimmune diseases currently lack curative options, with patients requiring lifelong standard-of-care management. Recent exploratory autologous CAR-T trials in autoimmune patients have provided proof of concept, giving Therona a clinical rationale to pursue in vivo CAR-T in this underserved population first.
✓Parallel US-China IND filing strategy: Therona targets Q4 2025 IND submissions simultaneously with the FDA and China's NMPA for TI-0032. Western pharma seeking Chinese biotech partnerships should note that nearly $7 billion in in vivo cell engineering deals since 2021 involved zero Chinese companies — licensing and collaboration structures, rather than acquisitions, are the practical pathway given current geopolitical and biosecurity constraints.

What It Covers

Beijing-based Therona Inc., founded in 2021, has built a circular RNA platform with three active clinical programs — prophylactic vaccine, therapeutic cancer vaccine, and in vivo CAR-T — while remaining largely unknown to Western pharma. CEO Lu Gao outlines the science, manufacturing approach, and dual US-China IND strategy for lead asset TI-0032.

Key Questions Answered

•Circular RNA stability advantage: Circular RNA uses natural nucleotides rather than chemical modifications like pseudouridine or 5-prime caps, allowing it to evade innate immune sensors naturally. This produces a longer half-life than linear mRNA in vivo, extending the therapeutic window and enabling sustained protein expression — a structural property that makes redosing feasible without reformulation.
•Scarless ligation manufacturing method: Therona's splint-free enzymatic ligation method splits the IRES sequence and places fragments on both sides of the coding region, allowing the linear precursor to self-fold and ligate under mild conditions. This eliminates splicing byproducts that require purification, reduces manufacturing complexity, and has already been validated under GMP for three clinical-stage products.
•In vivo CAR-T without lymphodepletion: TI-0032 delivers circular RNA via antibody-coated lipid nanoparticles that target T cells directly in the body. In nonhuman primates, the approach achieved complete B-cell depletion at low dose levels. Unlike autologous CAR-T, it requires no cell extraction, no lymphodepletion, and can be manufactured as an off-the-shelf product at a fraction of the cost.
•Autoimmune disease as primary CAR-T target: Therona prioritizes autoimmune indications over oncology for TI-0032 because B-cell-driven autoimmune diseases currently lack curative options, with patients requiring lifelong standard-of-care management. Recent exploratory autologous CAR-T trials in autoimmune patients have provided proof of concept, giving Therona a clinical rationale to pursue in vivo CAR-T in this underserved population first.
•Parallel US-China IND filing strategy: Therona targets Q4 2025 IND submissions simultaneously with the FDA and China's NMPA for TI-0032. Western pharma seeking Chinese biotech partnerships should note that nearly $7 billion in in vivo cell engineering deals since 2021 involved zero Chinese companies — licensing and collaboration structures, rather than acquisitions, are the practical pathway given current geopolitical and biosecurity constraints.

Notable Moment

Despite operating since 2021 with three clinical programs already running in humans, Therona had generated virtually no English-language press coverage before presenting at ASGCT in Boston — meaning the company reached clinical stage with GMP-manufactured circular RNA largely invisible to the Western biotech and investment community.

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Episode Transcript

Hello, and welcome to Beyond Biotech, the weekly podcast from Le BioTech. I'm Dylan Khesain, and this is episode 209 for the podcast. RNA therapeutics has had its defining moments, antisense oligonucleotides, psi RNA, and then, of course, mRNA, which went from a niche academic curiosity to the backbone of a global vaccine program in a matter of months. The next chapter may be circular RNA. Circ RNA is more stable than linear mRNA, longer lasting in the body and potentially redosable. And one company has quietly built what may be the most advanced independent circRNA platform in the world and with barely a single line of English language press coverage until now. My guest today is doctor Lou Gao, CEO of Therona Inc, a clinical stage biotech headquartered in Beijing and Shanghai. The company recently presented three posters at ASGCT in Boston, and their lead program has just entered a first in human trial. We're going to talk about the science, the clinical strategy, and why Western Pharma hasn't paid enough attention to what's being built in China. I hope you enjoy my interview with Lu Gao. Welcome to Beyond Biotech. Hello? Theron is a name that is probably a little bit unfamiliar to a lot of our listeners. Can you maybe start by telling us, well, who you are and what Therona does? Hi. I'm Lu Gao. I'm the CEO of Therona. So Serona is a clinical stage biotech company. We're, specialized in circular RNA technology. And, around that line, we have, enabled three different clinical trials, in prophylactic vaccine, therapeutic cancer vaccine, as well as in vivo CAR T. So Ronald was it was founded back in 2021 by professor Wensheng Wei. How did you come into the picture? What drew you into the field and to the company? Yeah. This is a long story. So I was trained as a microbiologist and immunologist, from University of Southern California. And I had my postdoc training, as well as a research faculty experience in UCSD. And after that I joined Roche, where I spent twelve years in infectious diseases, drug discovery, and clinical development where, we made a number of medicines and medicine candidates in clinical trials. And, so I was specialized in small molecule drug discovery and development as well as RNA field. I used to work with, siRNA as well as, antisense oligos. So with all this type of experience, I I later, worked with, pharmaceutical company, which is the largest China pharmaceutical Chinese pharmaceutical company, as, as a vice president as well as CEO for two of their subsidiary companies. And over there, had established a platform for their siRNA technology as well as, mRNA, technology platform that enabled, clinical development as well. So 2021, that was the time of, still within COVID nineteen, the pandemic, and many companies were investing in, RNA technology, especially in the linear mRNA field. So did I. And I, I had a lot of, hands on experience with linear …

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