InnoRNA Expands the Boundaries of mRNA Therapeutics: Targeting Rare Diseases, Chronic Conditions, and In Vivo CAR-T

On June 30, AbbVie announced it would acquire Capstan Therapeutics, a star player in the in vivo CAR-T space, for $2.1 billion, gaining access to CPTX2309, a potential first-in-class in vivo anti-CD19 CAR-T candidate currently in Phase I clinical trials for the treatment of B cell-mediated autoimmune diseases. Notably, AbbVie will also obtain Capstan’s proprietary tLNP platform technology. Leveraging the mRNA-tLNP approach, this platform enables the delivery of payloads such as mRNA to genetically engineer specific cell types in vivo.

Efficient and safe delivery technologies represent the core challenge in the clinical translation of mRNA therapies. In recent years, lipid nanoparticles (LNPs), as the mainstream delivery system, have achieved significant breakthroughs, directly facilitating the successful market approval of multiple RNA-based drugs, including siRNA therapeutics and mRNA vaccines.In 2018, the FDA approved Alnylam’s first small interfering RNA (siRNA) drug, Onpattro; in 2020, it approved Moderna’s and Pfizer/BioNTech’s SARS-CoV-2 mRNA vaccines, Spikevax and Comirnaty; and in 2024, it approved Moderna’s mRESVIA, the world’s first RSV mRNA vaccine. All of these products utilize lipid nanoparticle (LNP) delivery systems.

Shenzhen INNORNA Biotechnology Co., Ltd. (hereinafter referred to as “INNORNA”) is one of the few companies worldwide that has mastered the core technologies underlying lipid nanoparticle (LNP) design, and has globally deployed its mRNA-LNP technology platform with independent intellectual property rights. INNORNA has collaborated with numerous renowned biopharmaceutical companies both in China and abroad, becoming the first Chinese platform-based company to export its LNP platform technology overseas.

WhenThe world’s first bivalent RSV mRNA vaccine, China’s first shingles mRNA vaccineHow the Clinically Validated LNP-mRNA Platform Expands toTreatment of Rare and Chronic DiseasesProduct? With platform assets backed by independent global intellectual property rights, how does INNORNA achieve the global expansion of its LNP technology and foster international collaboration? Looking to the future, how will INNORNA seizeIn Vivo CAR-Tthe next big trend? At the inaugural stop of the “Hard Tech Media Tour: The Path of Innovation and Leapfrogging in China’s Biotechnology,” hosted by CAS Star, VCBeat spoke with Dr. Li Linxian, Founder and CEO of INNORNA.

Dr. Linxian Li, Founder, Chairman, and CEO of INNORNA. He holds a Ph.D. from Heidelberg University in Germany and completed his postdoctoral research at the Massachusetts Institute of Technology (MIT) in the United States.

Dr. Li Linxian has dedicated many years to the development of nucleic acid therapeutics and lipid nanoparticle (LNP) delivery technologies. During his doctoral studies, he focused on the chemical structures of liposomes. As a postdoctoral fellow at MIT, he studied under Professor Robert Langer, a renowned expert in nucleic acid drug delivery and a technological founder of Moderna. His research primarily centered on the design and investigation of ionizable lipids, a core component of LNPs. He has published numerous findings in top-tier international journals such as *Nature Biotechnology*. Dr. Li is hailed as a pioneer in exploring the therapeutic potential of mRNA and providing innovative tools to accelerate the development of novel biomaterials to address global healthcare challenges.

Based on years of research, Dr. Linxian Li successfully developed a diversity-oriented library of LNP delivery vectors and founded INNORNA in late 2019, making it one of the few companies globally with core innovative capabilities in LNP technology. To date, the company has filed over 80 invention patents and established collaborations with renowned domestic and international enterprises such as BeiGene.Dr. Li Linxian was named to MIT Technology Review’s “35 Innovators Under 35” in China in 2017 for developing next-generation lipid nanoparticle (LNP) technology for mRNA delivery, standing as the sole representative from the pharmaceutical industry; he was listed among Fortune China’s “40 Business Elites Under 40” in 2023 and included in Citeline’s “In Vivo’s 2024 Rising Leaders” in 2024.

RNA can be programmed to produce antigens, thereby eliciting immune responses against tumors and infectious diseases, or to generate functional proteins that are impaired due to loss of gene function or mutations. Lipid nanoparticles (LNPs), as a currently mature and widely recognized delivery system, can effectively deliver mRNA to specific tissues or cells in vivo.

Classic LNP formulations include ionizable lipids, cholesterol, helper lipids, and polyethylene glycol (PEG)-conjugated lipids. Ionizable lipids play a key role in the encapsulation of mRNA into LNPs and are critical for facilitating endosomal escape of mRNA into the cytoplasm after cellular entry. Structurally, the design space for ionizable lipids is extensive, and minor chemical modifications can significantly impact their biological functions.Notably, the LNP formulations of the four drugs and vaccines approved by the FDA all contain unique ionizable lipids.

Since its inception, INNORNA has chosen to independently build its LNP technology platform. It has currently established a library of over 5,000 ionizable lipids for screening LNP vectors suitable for different therapeutic scenarios. Its robust LNP technology stems from Dr. Linxian Li’s more than ten years of experience in LNP delivery systems and mRNA drug development.

During his doctoral studies at Heidelberg University in Germany, Dr. Linxian Li focused his research on RNA drug delivery technologies. Subsequently, he conducted postdoctoral research in the laboratory of Professor Robert Langer at the Massachusetts Institute of Technology (MIT)—a co-founder of Moderna and one of its scientific pioneers—where he delved into the large-scale construction of amino lipid libraries and high-throughput screening technologies.

Dr. Li Linxian stated, “LNP research during the MIT era tended to focus on combinatorial chemical lipid libraries. In contrast, the INNORNA team constructed diversity-oriented lipid libraries with different core structures based on distinct underlying chemical approaches.” The diversity of molecular structures is key to discovering lipids with novel functions.Compared with traditional combinatorial compound libraries, diversity-oriented lipid libraries exhibit greater molecular diversity, significantly increasing the likelihood of discovering lipids with novel functions, thereby enhancing the overall efficiency and success rate of the LNP platform.

Leveraging a diversity-oriented lipid library, the platform analyzes and optimizes synthetic structures and activity data to simulate the delivery and therapeutic efficacy of nucleic acid drugs via high-throughput screening. This process identifies diverse ionizable lipid structures with varied functionalities—such as distinct targeting capabilities, reduced immunogenicity, and lower toxicity—to meet specific delivery requirements.

Dr. Li Linxian introduced that shortly after the establishment of INNORNA, the COVID-19 pandemic struck. Consequently, the company initially focused on developing and validating LNP technology for vaccine delivery, and built up end-to-end mRNA-LNP development capabilities through several infectious disease vaccine projects. Currently,Respiratory syncytial virus (RSV) vaccine IN006 has entered Phase II clinical trials in China, and herpes zoster (HZ) vaccine IN001 has completed Phase I clinical studies in the United States and Australia.Among these, IN006 is the world’s first bivalent RSV mRNA vaccine to enter clinical development, as well as the first domestically produced RSV vaccine approved for clinical trials in China; IN001 is the first herpes zoster mRNA vaccine product approved for clinical trials in China, demonstrating broad clinical potential.

Following the initial proof of concept for its vaccine, the development of therapeutic products marks a pivotal transformation for INNORNA as a platform-based biotech company.

Dr. Li Linxian described mRNA therapy as an “elegant” intervention: “It offers a precise and programmable approach that instructs human cells to transiently produce desired therapeutic proteins, without the need for permanent genetic modification or reliance on viral vectors. In essence, this represents a entirely new therapeutic paradigm—directly intervening in disease processes at the level of genetic messengers, rather than merely at the protein level.” Meanwhile, as a critical bridge connecting DNA and proteins, mRNA holds promise for addressing the druggability limitations of existing targets, exploring the targeting of approximately 85% of the undruggable protein-coding genome, and thereby partially resolving the dilemma of traditional drugs being “untargetable” and “undruggable.” Dr. Li Linxian stated,In theory, mRNA can express any protein and has the potential to prevent or treat nearly all diseases caused by protein dysfunction, including infectious diseases, cancer, autoimmune disorders, and certain rare diseases.

Specifically, the core elements and coding sequences of mRNA determine its binding stability, thereby influencing the efficiency and duration of protein translation per unit time. INNORNA’s proprietary mRNA platform has established a library of untranslated region (UTR) sequences and developed proprietary Poly-A technology. Through nucleic acid sequence optimization, the platform enhances both the efficiency and longevity of protein translation.

As R&D efforts deepen, the INNORNA team is also expanding the application boundaries of LNP delivery. During systemic administration, LNPs primarily accumulate in the liver, making the liver a natural starting point, with subsequent expansion to extrahepatic parenchymal organ delivery, includingHepatic delivery (protein replacement therapy/in vivo gene editing), immune cell delivery (ex vivo CAR/in vivo CAR), adipose/muscle delivery (weight loss/muscle-related diseases), and local delivery (pulmonary/intraocular/CNS/intratumoral).

“Our primary objective is to assess the differentiation and maturity of our technology, identify the pipeline types best suited for our mRNA technology platform, and then address unmet clinical needs, market potential, and scientific validation for those pipelines. We believe our technology platform has reached this stage, which is why we have focused on developing therapeutic products for rare diseases and chronic conditions,” said Dr. Li Linxian.

It is reported that INNORNA currently has four mRNA-based therapies for rare diseases in development, targeting Wilson’s disease (WD), progressive familial intrahepatic cholestasis type 3 (PFIC-3), progressive familial intrahepatic cholestasis type 2 (PFIC-2), and homocystinuria (HCU). All four programs have received Rare Pediatric Disease Designation (RPDD) and Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA).

It is evident that INNORNA’s initial focus in its therapeutic pipeline is on liver-centric indications, aligning with the characteristic accumulation of systemically delivered lipid nanoparticles (LNPs) primarily in the liver. In fact, hepatic and other tissue deliveries of mRNA are predominantly administered via intravenous injection, which involves two major challenges: safety and targeting. “The dosages for therapeutic products are significantly higher than those for vaccines, often exceeding them by more than 1,000-fold. Consequently, regulatory reviews exercise great caution regarding clinical safety, including assessments of the immunogenicity, tissue distribution, and targeting specificity of the delivery vectors. In the field of chronic diseases, long-term safety concerns arise from even higher drug doses, repeated administrations, and in vivo metabolic cycles,” noted Dr. Li Linxian.

In 2025, INNORNA publicly unveiled its chronic disease pipeline candidate IN026, marking the company’s formal entry into the chronic disease sector—where effective treatments remain scarce and significant unmet clinical needs persist—and establishing it as one of the pioneering enterprises globally to deploy mRNA therapeutics for the development of treatments for specific major chronic diseases.

In fact, this growth trajectory is evident in the field of oligonucleotide therapeutics: within the realm of rare disease treatment, oligonucleotide drugs have achieved a disruptive breakthrough from scratch. Spinraza, indicated for spinal muscular atrophy (SMA), has enabled pediatric patients receiving early intervention to survive into adulthood, surpassing the historical prognosis of death before age two. Despite an annual treatment cost of approximately $500,000, Spinraza has become the first oligonucleotide drug globally to achieve annual sales exceeding $2 billion.

In the field of chronic disease management, the long-acting interventional properties of small nucleic acid drugs have shone brightly in controlling hyperlipidemia and hypertension. Inclisiran has reduced the annual dosing frequency for hyperlipidemia patients from 73 times with statins to just twice, improving treatment adherence by 36-fold and driving a 112% increase in its sales revenue in 2024.

By targeting encoded proteins, mRNA enables controlled expression of therapeutic targets, whether for systemic protein replacement or immunomodulation via receptors such as T-cell receptors (TCRs) and chimeric antigen receptors (CARs). Based on this underlying principle, INNORNA has extended its LNP-mRNA application scenarios to in vivo CAR-T therapy.

In vivo CAR-T therapy utilizes lipid nanoparticles (LNPs) to directly deliver mRNA to T cells in the bloodstream, enabling transient expression of chimeric antigen receptor (CAR) molecules and eliciting tumor-specific immunity. This approach circumvents the cumbersome and costly ex vivo engineering and expansion steps, thereby achieving "instant engineering, immediate treatment."

Dr. Li Linxian believes that,In vivo CAR-T therapy transforms highly personalized, customized treatments into off-the-shelf drugs. It can essentially be viewed as a more accessible and affordable mRNA-based therapeutic, significantly shortening the production cycle and eliminating the need for lymphodepleting preconditioning. This approach is expected to substantially reduce manufacturing costs, potentially bringing CAR-T therapy within the financial reach of most patients.

The exploration of in vivo CAR-T therapy represents an inevitable path toward the maturation and expansion of platform technologies. Dr. Li Linxian emphasized, “What we have always been seeking is to identify the optimal applications for the LNP-mRNA technology platform. From a long-term strategic perspective, INNORNA is a platform-driven biotechnology company, rather than a traditional pharmaceutical enterprise.” Following the same logic, global expansion and strategic collaborations are also exploratory efforts to broaden R&D pathways and achieve self-sustaining growth.

In 2022, INNORNA andBeiGeneAchieved a global strategic partnership to jointly advance the R&D of several mRNA-LNP projects, with INNORNA granting BeiGene a non-exclusive license to its LNP platform technology. In 2023, INNORNA andA U.S.-headquartered MNCAchieved Significant Collaboration, BecomingChina's First LNP Platform Technology Goes Global.

“By engaging with diverse partners, the team aims to jointly explore new application scenarios. In the long term, our internal resources for developing such scenarios are limited; however, the LNP platform technology holds vast potential. If hundreds of companies commit to exploration, fostering an industrial chain and ecosystem, mRNA technology, its indications, applications, and underlying basic science will all experience rapid advancement,” said Dr. Li Linxian.

Previously, INNORNA had completed four rounds of financing, with a cumulative total of $150 million. The company boasts nearly 10,000 square meters of R&D space and employs over 150 staff members, more than 80% of whom are engaged in research and development. Meanwhile, INNORNA has established mature CMC processes, setting up a CMC process scale-up and pilot production center as well as a liposome base in Shenzhen, thereby possessing cGMP-compliant liposome/formulation manufacturing capabilities.

As foundational technological innovations move toward commercialization and practical implementation, platform-based operations signify the exploration of more diversified development paths and business models. However, returning to the fundamentals—addressing critical “chokepoint” issues and building technical moats aligned with global standards—remains the enduring truth for innovations to go global and capture market share.