Exclusive: Farewell to Cations! Lingshuo Biotechnology Secures RMB 40 Million Seed Funding, Pioneering a New Track for Global "Non-Ionic" Nucleic Acid Delivery Technology

A Chinese solution is emerging to address the challenges of nucleic acid drug delivery.

While mainstream global technologies remain trapped by the limitations of cationic lipids, including immune inflammation and liver-targeting restrictions, Xi'an Lingshuo Biotechnology Co., Ltd. (hereinafter referred to as Lingshuo Biotechnology) has embarked on a fundamentally distinct approach — non-ionic delivery.

Its globally pioneering NC-TNP platform achieves high-efficiency loading through hydrogen bonding rather than relying on positive charges to bind nucleic acids, thereby fundamentally circumventing the safety risks associated with traditional LNPs.

More noteworthy than the "non-ionic" feature itself is that this platform inherently possesses two delivery capabilities hard to replicate with existing technologies. Without any modification, it can precisely target the spleen after injection, unlocking new possibilities for cutting-edge therapies such as in vivo CAR-T and autologous immune regulation. Meanwhile, it enables transdermal delivery, bringing non-invasive treatment for hereditary deafness and nucleic acid cosmetics from concept to reality.

Non-ionic, spleen-targeted, transdermal delivery — These three labels collectively outline the unique profile of NC-TNP as the next-generation global nucleic acid delivery platform.

VCBeat learned exclusively that Lingshuo Biotechnology has recently closed a RMB 40 million seed financing round. The round was led by Shaan Tou Growth Fund, with Xi'an Caijin participating as a follow-on investor. The proceeds will be mainly allocated to advancing pipeline R&D, team expansion, hardware infrastructure development and technical upgrades of its delivery platform, accelerating the clinical translation of its core products.

As nucleic acid drugs such as mRNA and siRNA gradually enter the commercialization stage, delivery technology has become a key factor determining the application boundaries of nucleic acid therapies.

At present, the global nucleic acid delivery field mainly relies on two major technical systems: LNP (Lipid Nanoparticle) and GalNAc (N-Acetylgalactosamine). Among them, LNPs have enabled the large-scale application of mRNA vaccines, while GalNAc is widely adopted for the development of liver-targeted siRNA therapeutics.

Nevertheless, existing delivery systems still face challenges including immunogenicity, limited tissue targeting scope, insufficient duration of in vivo expression, and high production costs. Particularly for extrahepatic organ delivery, achieving delivery with higher precision, improved safety and greater industrialization potential remains a core bottleneck urgently needing breakthroughs for the global nucleic acid therapeutics industry.

Breaking the boundaries of traditional delivery systems to develop a new-generation nucleic acid delivery platform featuring enhanced safety and precise, accessible extrahepatic targeting has become a key direction for further advancing the development of nucleic acid therapeutics.

Lingshuo Biotechnology is strategically positioning itself to address this industrial bottleneck.

The story of Lingshuo Biotechnology began with a foundational research project that has been ongoing for 13 years.

Professor Deng Hongzhang, the founder, has long focused on the design of nanodelivery materials and research on nucleic acid drug delivery. He earned his Ph.D. in Materials and Chemical Engineering from Tianjin University and conducted postdoctoral research at the U.S. National Institutes of Health (NIH). He currently serves as a Professor and Doctoral Supervisor at Xidian University.

During the research on traditional nucleic acid delivery systems, the team gradually realized that although existing cationic delivery systems have promoted the rapid development of nucleic acid drugs, their underlying mechanisms have also introduced new limitations.

"Traditional cationic lipids primarily rely on electrostatic interactions to bind nucleic acids, but this approach is prone to inducing immune activation and cytotoxicity." Deng Hongzhang stated in an exclusive interview when discussing the limitations of existing delivery technologies.

Based on this assessment, the team began to move beyond the traditional electrostatic binding approach — instead of using positive charges, they employed functional groups to form binding interactions with the phosphate backbone of nucleic acids for nucleic acid loading.

In 2023, the team completed the development of a novel non-cationic mRNA delivery system, with the related findings published in "PNAS". However, the publication of the paper was only the first step. What determined Deng Hongzhang to step out of the laboratory was not only the value of the technology itself, but also a team with clinical expertise.

Professor Wang Shan, a co-founder from Xijing Hospital, has long focused on mRNA sequence optimization and the delivery mechanisms of nucleic acid drugs, while also possessing experience in clinical trials for innovative drugs. "Professor Deng specializes in vectors, while I excel in nucleic acids; together, we cover the two most critical knowledge systems in nucleic acid drug development. Coupled with my background in clinical trials, this allows us to adopt an end-to-end approach from the outset, clearly understanding what patients truly need."

The two first connected through scientific research collaboration. Professor Wang Shan recalls that she initially approached Professor Deng Hongzhang with her own research needs, and Professor Deng generously provided the vector materials without reservation. In subsequent collaborations, the team accidentally discovered that this vector not only naturally targeted the spleen via intravenous injection but also enabled transdermal delivery by penetrating the skin surface — a feat no other vector worldwide has achieved to date. "Upon observing this phenomenon, Professor Deng and I were thrilled and engaged in extensive discussions." It was precisely these personally verified data that convinced Professor Wang Shan to wholeheartedly commit to entrepreneurship.

In 2025, Lingshuo Biotechnology was officially established, advancing non-ionic nucleic acid delivery technology from research achievements to the drug development stage.

Centered on the foundational technology direction of "non-ionic," Lingshuo Biotechnology has built the world's only non-cationic delivery platform: NC-TNP.

Unlike traditional LNPs that rely on electrostatic adsorption between cationic lipids and nucleic acids, NC-TNP employs a non-ionizable design, forming stable hydrogen bonds between functional groups and the phosphate groups of nucleic acids to achieve efficient loading and delivery of nucleic acid molecules.

This shift in the underlying mechanism enables NC-TNP to address several long-standing core issues associated with traditional delivery systems.

First, address the safety challenges of traditional delivery systems.

In the past, cationic lipid systems have driven the rapid development of nucleic acid therapeutics; however, their positively charged structures may also lead to issues such as non-specific immune activation, inflammatory responses, and cytotoxicity, thereby limiting the application of certain nucleic acid drugs in long-term administration and complex disease scenarios.

To address this issue, NC-TNP employs a non-ionizable design to reduce nonspecific interactions between the carrier and cell membranes as well as the immune system, thereby further expanding the safety window for the application of nucleic acid therapeutics.

According to the team, this platform does not contain traditional cationic structures, which is expected to reduce the risk of systemic inflammatory responses. It is particularly suitable for disease scenarios requiring long-term management or repeated dosing, such as rare diseases and chronic conditions.

Secondly, break through the liver limitations of traditional delivery systems.

Currently, nucleic acid drugs marketed globally remain largely concentrated in a limited number of therapeutic applications. Among these, GalNAc technology primarily relies on hepatocyte receptors to achieve liver targeting, while LNP systems are also predominantly directed toward hepatic delivery.

However, as nucleic acid therapeutics expand beyond liver diseases into fields such as genetic disorders, oncology, and autoimmune diseases, achieving precise extrahepatic delivery has become a key bottleneck restricting industry development. The emergence of the NC-TNP platform offers a novel technological approach to this global challenge: natural spleen targeting and transdermal delivery.

Unlike traditional strategies that rely on ligand modification to achieve extrahepatic targeting, the splenic targeting capability of NC-TNP stems from the "innate properties" of its non-ionizable design. After intravenous injection, this carrier can automatically home to the spleen without any additional modification, enabling precise delivery of nucleic acid drugs.

The critical nature of this capability stems from the spleen's unique position. As the largest peripheral immune organ in the human body, the spleen serves as a major habitat and functional regulatory hub for immune cells such as T cells, B cells, and NK cells. The ability to precisely deliver nucleic acid drugs to the spleen enables direct in vivo reprogramming of immune cells — representing the core breakthrough for next-generation cell therapy strategies such as in vivo CAR-T and CAAR-T.

"Currently, all globally approved CAR-T therapies require ex vivo modification of immune cells before reinfusion, a process that is complex, costly, and entails long patient waiting times," said Deng Hongzhang. "If we could perform this process directly in vivo, the threshold for cell therapy would be significantly lowered."

Leveraging this natural spleen-homing capability, Lingshuo Biotechnology has advanced its LS003 in vivo dual-target CAR-T program and LS004 in vivo CAAR-T program, targeting hematologic malignancies and autoimmune diseases such as myasthenia gravis, respectively, to explore a novel therapeutic paradigm of "injection-as-treatment."

If spleen targeting represents the "depth" of NC-TNP in the realm of organ-level precision delivery, then its transdermal delivery capability constitutes the "breadth" that expands the boundaries of its applications.

Conventionally, nucleic acid drugs are considered to have high molecular weights and strong hydrophilicity, making them nearly incapable of penetrating the stratum corneum barrier of the skin. Mainstream delivery systems rely on injection-based administration — whether intramuscular, subcutaneous, or intravenous infusion — which inevitably leads to poor patient compliance, high storage and transportation costs, and the need for professional medical personnel to administer the treatment. These limitations also hinder the broader adoption of nucleic acid drugs in scenarios such as chronic disease management and home-based therapy.

Meanwhile, the NC-TNP platform, leveraging its non-ionic molecular design, has unexpectedly opened another avenue. In early studies, the team discovered that this carrier could transport nucleic acid molecules across the skin barrier without the need for physical assistance such as microneedles or electroporation, thereby achieving local or systemic drug delivery. This finding represents a first in the global field of nucleic acid delivery.

"When we saw the transdermal data, Professor Deng and I were extremely excited, as this had never been reported in any literature," recalled Professor Wang Shan.

Leveraging this disruptive capability, NC-TNP demonstrates significant potential in non-invasive drug delivery scenarios. In the field of genetic disorders, it enables the treatment of hereditary deafness via topical administration through the external auditory canal, thereby avoiding the risks associated with invasive surgeries. In the consumer health sector, it supports a product line of nucleic acid-based cosmetics — such as transdermal delivery of mRNA encoding collagen to promote anti-aging effects, or delivery of tyrosinase siRNA to achieve skin-whitening benefits. In broader therapeutic contexts, transdermal delivery opens up new possibilities for "patch-style" nucleic acid therapies for conditions requiring long-term medication, such as diabetes and chronic pain.

From invasive injections to non-invasive transdermal delivery, NC-TNP is not merely an upgrade in delivery technology but has the potential to redefine the administration of nucleic acid therapeutics.

"Spleen-targeting enables us to develop injectables for treating major diseases, while transdermal delivery allows us to create non-invasive products that reach a broader population — only by advancing both strategies in tandem can the platform's value be truly maximized," summarized Deng Hongzhang.

Third, achieve compatibility with multiple types of nucleic acid drugs.

Unlike some traditional delivery systems that primarily target specific types of nucleic acid molecules, the NC-TNP platform is compatible with various nucleic acid drug formats, including mRNA and siRNA.

This means that the same delivery platform can support both functional protein expression via mRNA and silencing of abnormal gene expression using siRNA, providing foundational technological support for multiple therapeutic areas, including genetic disorders, cancer, autoimmune diseases, and metabolic diseases.

For platform-based biotech companies, this multi-nucleic acid type compatibility also provides greater technical space for subsequent pipeline expansion.

Fourth, balance technological innovation with industrialization needs.

In addition to delivery efficacy, industrialization capability is also a critical factor determining the commercial viability of nucleic acid therapeutics.

Traditional complex nanodelivery systems often face challenges such as intricate formulations and difficulties in scale-up manufacturing, whereas NC-TNP employs a two-component design with a simpler structure, facilitating process development and large-scale production.

Leveraging these capabilities, the NC-TNP platform has established core advantages including high safety with low inflammatory response, precise extrahepatic delivery, compatibility with diverse types of nucleic acids, and low cost with ease of mass production.

The value of a technology platform must ultimately be validated through its clinical pipeline.

Leveraging its NC-TNP non-ionic nucleic acid delivery platform, Lingshuo Biotechnology has not confined itself to a single indication. Instead, it has established a diversified pipeline of nucleic acid therapeutics targeting disease areas poorly served by conventional delivery systems, including genetic disorders, oncology, autoimmune diseases, and cardiovascular conditions.

From protein replacement for genetic diseases and tumor mRNA vaccines to cutting-edge therapeutic strategies such as in vivo CAR-T / CAAR-T, the company aims to explore the application boundaries of nucleic acid technology across diverse disease areas via a unified delivery platform.

Among them, the LS001 hereditary hearing loss program serves as a key application demonstrating the transdermal delivery capacity of NC-TNP.

Hereditary deafness is one of the more common genetic disorders in the pediatric population, and current therapeutic options for specific gene defects remain limited. This project leverages the transdermal delivery capability of NC-TNP to explore non-invasive gene replacement therapy.

"We aim to prioritize the field of rare pediatric diseases, where clinical needs are well-defined, thereby accelerating the development of innovative therapies," said Wang Shan.

Currently, the project has advanced to the PCC (Preclinical Candidate Confirmation) stage, with plans to further pursue dual IND filings in both China and the United States.

In the oncology field, the company has initiated the LS002 mRNA vaccine project for esophageal squamous cell carcinoma.

China is one of the regions with a high incidence of esophageal squamous cell carcinoma globally, yet patients with advanced-stage disease still face limited treatment options. Leveraging the nucleic acid delivery capability of NC-TNP, this project aims to activate patients' own immune systems via mRNA technology, thereby achieving more precise cancer therapy.

According to the company, the project has entered the Investigator-Initiated Trial (IIT) phase. Early clinical exploration has demonstrated sustained benefits in subjects, and follow-up large-scale clinical studies are currently being advanced.

Furthermore, leveraging the delivery potential of NC-TNP to immune-related tissues, Lingshuo Biotechnology has further expanded its layout into the fields of in vivo CAR-T and in vivo CAAR-T therapies.

Traditional CAR-T therapy requires the ex vivo collection, modification, and expansion of immune cells, a process that is complex and costly, thereby limiting its application in a broader patient population.

The LS003 in vivo dual-target CAR-T program leverages spleen-targeted delivery capacity to directly deliver CAR mRNA to patients' endogenous T cells and achieve in vivo reprogramming of immune cells. This technical approach is expected to reduce the manufacturing complexity of cell therapy and expand the application scope of CAR-T in autoimmune diseases and hematological malignancies.

The LS004 in vivo CAAR-T program targets autoimmune diseases such as myasthenia gravis, exploring novel therapeutic modalities via in vivo engineered immune cells.

In the field of cardiovascular diseases, the company advances the LS005 targeted therapy program for atherosclerotic plaques.

This project utilizes siRNA technology to intervene in disease-related targets, exploring precision therapeutic strategies for atherosclerotic plaques. This direction also marked the important starting point of the early scientific collaboration between Deng Hongzhang and Wang Shan, and has currently completed validation in the animal experimental phase.

From the perspective of overall pipeline design, Lingshuo Biotechnology does not simply replicate a single technological route; instead, it matches different disease needs with the varying delivery capabilities of NC-TNP.

From non-invasive administration (LS001) to intramuscular injection (LS002), and further to intravenous injection (LS003–LS004), the safety validation of the pipeline progresses in a stepwise manner. "Safety is progressively enhanced, from non-invasive to intramuscular injection, and then to intravenous injection," explained Wang Shan, outlining the design logic of the pipeline.

For an early-stage biotech company, possessing a foundational technology is merely the first step; the ability to continuously translate platform capabilities into clinical assets and commercial value determines the enterprise's long-term growth potential.

In addition to innovative drug development, Lingshuo Biotechnology is also exploring the industrial application of nucleic acid technologies in the consumer health sector based on its NC-TNP platform.

Leveraging transdermal delivery capabilities, the company expands into nucleic acid cosmetic products. Its pipeline encompasses the development of mRNA collagen, tyrosinase siRNA and other products, exploring the use of nucleic acid technology to deliver anti-aging, skin brightening and other functionalities.

According to the company, the related products have completed efficacy validation. "The cycle for cosmetics and technical services is relatively short. We hope to generate cash flow to further support the R&D of nucleic acid drugs," said Wang Shan.

Furthermore, the company also plans to conduct technical services and vector development centered on its delivery platform, further expanding the industrial application value of the NC-TNP platform.

"We are not just building a delivery platform; we are developing pharmaceuticals around the platform," said Deng Hongzhang.

From foundational technology R&D to multi-domain pipeline layout, and further to the exploration of commercialization scenarios, Lingshuo Biotechnology aims to build not just a delivery technology, but a platform system capable of continuously incubating innovative nucleic acid assets.

For Lingshuo Biotechnology, NC-TNP is not a standalone technology, but rather a critical foundation for exploring next-generation nucleic acid delivery systems.

Currently, the company has conducted validations in areas such as spleen targeting and transdermal delivery, and aims to further expand into more complex tissues and organs.

"We are still exploring directions such as myocardial targeting and brain neuron targeting, including how to breach the blood-brain barrier to deliver nucleic acid drugs to the central nervous system," stated Wang Shan.

From the team's perspective, organ-level precise delivery remains a core challenge that has not yet been fully resolved in the global field of nucleic acid therapeutics. In the future, Lingshuo Biotechnology aims to leverage its non-ionic delivery platform to continuously expand the boundaries of delivery capabilities and explore more therapeutic scenarios that are difficult to address with conventional systems.

Deng Hongzhang has a clear long-term positioning for the company: to build an indigenous and original next-generation nucleic acid delivery technology system in China.

"We should develop China's own delivery vectors rather than simply following existing technological pathways. Just as with new energy vehicles, China should — and has the capacity to — create original technologies with global competitiveness," said Deng Hongzhang.