Chinese Academy of Sciences

Five people with beta thalassemia who had their blood stem cells genetically altered no longer require regular blood transfusions to stay healthy. Their Chinese-made treatment is likely to be cheaper, and perhaps safer and more effective, than its American counterparts. Developed by CorrectSequence Therapeutics, the therapy employs a novel form of CRISPR base editing designed to change a single letter of DNA with almost no unwanted and potentially dangerous off-target edits. The Shanghai-based company told Endpoints News that the first patient treated has now been transfusion-free for nearly two and a half years. The study of the five patients, published Wednesday in Nature , arrives as interest grows among Western drugmakers in experimental therapies made in China. And the new study suggests China will continue to become a bigger competitor even for the most cutting-edge medicines. “This is a reflection of the tremendous acceleration in the research that’s coming from China — the quality and the quantity,” Mitchell Weiss, chair of the hematology department at St. Jude Children’s Research Hospital who wasn’t involved in the study, told Endpoints. “It doesn’t look like they’re skipping corners.” Correctseq’s therapy boosts levels of fetal hemoglobin to make up for a deficiency in the adult form of the oxygen-ferrying protein. Two commercial medicines, Casgevy and Zynteglo — made by US companies — do the same thing in different ways. But CRISPR Therapeutics and Vertex Pharmaceuticals charge $2.2 million for Casgevy, and bluebird bio charges $2.8 million for Zynteglo. Neither treatment is approved in China, and the high price tags of those drugs and other multimillion-dollar gene therapies are spurring several startups in the country to develop more affordable versions . “They’re not depending on US technologies,” Weiss said. “They’re doing it themselves because they can now, and because they can probably do it cheaper.” Correctseq CEO Xiaodun Mou told Endpoints that it was too soon to discuss the price or commercialization of the treatment. But labor, manufacturing, research and clinical trials can all be cheaper and faster in China. Co-founder Jia Chen told Endpoints he believes the therapy will be safer and more effective too. Although it’s hard to make direct comparisons, in addition to fewer off-target edits, the trial results suggest its edited cells engrafted in patients more quickly than they did with the American therapies. “All of the patients have been clinically cured, because they have been independent of the transfusion for at least one year,” Chen said. “It was thrilling to see all these patients treated. And every time they were released from hospital, we went to meet them, and they always hugged me and cried, because it’s a release for them.” Weiss was impressed but wants to see more patients treated and followed for at least five years. “A cure means that it lasts, and so a conservative clinician would not say it’s a cure,” he said. “But this promises to be a cure.” Chen’s background in studying how DNA is naturally repaired in cells helped him quickly realize both the promise and problems of emerging gene editing technologies. After finishing a PhD at the Chinese Academy of Sciences in 2009, Chen moved to the US for a postdoctoral fellowship at the NIH where he made a surprising discovery . When cells attempt to correct a single-strand break in DNA — the kind of damage that arises daily from the wear and tear of life — an enzyme called APOBEC can hijack the process and turn one letter of the genetic code into another. That mutagenic process might contribute to aging, disease and possibly even evolution. In 2014, Chen moved back to China to start his own lab at ShanghaiTech University. As he continued to study APOBEC, another group of scientists in the US fused the enzyme to Cas9, the molecular scissors of CRISPR. David Liu’s lab at the Broad Institute used a dulled version of those scissors to nick a single strand of DNA at a precise spot, prompting the piggybacked APOBEC enzyme to swoop in and do its work. Liu called the method base editing . It gave scientists a way to precisely fix or introduce genetic typos. It wasn’t perfect though. The enzyme would sometimes latch onto other strands of DNA totally independent of CRISPR. That posed a problem for turning the tool into a medicine. “We want to really eliminate off-target mutations, because for a therapy, safety is a priority,” Chen said. Back in Shanghai, his lab was devising a solution. Chen discovered a protein that naturally inhibited APOBEC. The lab tethered the enzyme and its inhibitor together to prevent the base editing tool from working even when it reaches its target site. Then it created a second molecular machine that would follow closely behind, break the tether, release the inhibitor and allow APOBEC to make its edit — but only when both systems are locked in place. It was like two-factor authentication for gene editing. Chen christened the technology transformer base editing . Chen co-founded Correctseq with three colleagues in 2020 to develop therapies based on the technology. The following year, the startup quietly raised close to $40 million in a Series A funding round led by Lilly Asia Ventures and Boyu Capital. Mou told Endpoints the company has now raised about $60 million total. Although Mou is focused on treating patients in China first, she said that the company has filed patent applications across Asia, Africa, Europe and the US and is interested in eventually taking the company’s drugs global. “We want our technologies to benefit more patients,” she said. Correctseq treated its first patient in October 2023. The first five patients have all been transfusion-free for over a year now. The company has since treated at least 10 more and is planning a Phase 2 trial that could enroll about 20 more people. Data from the first five patients came a week after two papers appeared in The New England Journal of Medicine describing comparable studies sponsored by Beam Therapeutics and Editas Medicine , both based in Cambridge, MA. The three companies used different forms of CRISPR to achieve similar results: the elevation of fetal hemoglobin. Fetal hemoglobin production normally shuts down in infancy due to a protein called BCL11A. Casgevy, the commercialized CRISPR therapy, effectively shuts down that repressor — a double-negative that allows blood cells to make fetal hemoglobin again. Beam, Correctseq and Editas have taken a slightly different approach that alters the patch of DNA that the repressor protein binds to — the HBG1 and HBG2 promoters. The result, enhanced fetal hemoglobin production, is about the same, but allows BCL11A to carry on with its other roles in the cell. The ability to produce fewer off-target edits is “an important advance,” said Vijay Sankaran, a physician and blood cell biologist at Boston Children’s Hospital whose research on BCL11A helped lay the groundwork for Casgevy . “[It] should provide additional opportunities to target the BCL11A axis in potentially a safer and more effective manner.” Weiss cautioned that it’s too soon to know if the technical differences in the therapies will make a difference for patients. “Base editing has theoretical safety advantages. But we don’t know if they translate to real safety advantages,” he said. “And the only way to know which method for manipulating the genome is better is to follow these patients out for a long time.” The patients did not appear to have any side effects related to the base editing treatment, although they all suffered from severe anemia, leukopenia, neutropenia and thrombocytopenia from the chemotherapy conditioning used to wipe out their bone marrow and make room for the engineered cells. Most companies that are working on new treatments for the two blood diseases have pivoted to a so-called in vivo approach that would edit the patient’s blood cells directly in their body . If successful, such an infusion could eliminate complex laboratory work and the grueling need for chemotherapy preconditioning. “It’s our future direction, and my lab is working on that,” Chen said. Numerous other companies abandoned promising therapies for beta thalassemia and sickle cell disease after Casgevy was approved, including Editas , which has shifted its focus to more common diseases . But Mou said that Correctseq is committed to its CS-101 program and noted that there are more than 300,000 patients with beta thalassemia in China — three times more than the number with sickle cell disease in the US. “We definitely want to bring this product to the market,” she said. “We’re expecting that by the time CS-101 enters the market, there will be a more systematic and scientific system to guide us to a more reasonable price.” Weiss thinks there’s room for more beta thalassemia and sickle cell treatments. But he also believes technology is no longer the limiting factor for gene therapies, as evidenced by Editas’ withdrawal from the field. “That they’re dead in the water reflects the bigger problem with gene therapy: that it’s not commercially viable,” Weiss said. “Our technology has surpassed our society’s ability to deliver it efficiently.” If China is able to make gene therapies that are just as safe and effective as US medicines, but offer them at a lower price, it could shake up the system globally. “I think in the end, we’re going to find that there are going to be many treatments that are going to be similar in their efficacy. It’s the whole package that matters,” Weiss said.

SHANGHAI, April 9, 2026 /PRNewswire/ -- Shanghai Ark Biopharmaceutical Co., Ltd. ("ArkBio") today announced that the first cohort of healthy volunteers has been dosed in a phase I clinical trial of AK0406, a novel long-acting antiviral drug-Fc conjugate (ADFC) drug for influenza infection, following approval by the Human Research Ethics Committee (HREC) in Australia. This milestone marks the first-in-human (FIH) evaluation of AK0406 and an important step in the global clinical development of ArkBio's influenza pipeline. AK0406 is a next-generation, long-acting ADFC candidate discovered and developed by ArkBio. By conjugating a potent small-molecule antiviral to the antibody Fc domain, AK0406 is designed to combine the direct antiviral effect of the payload with Fc-mediated immune clearance and an extended half-life. Preclinical data show that AK0406 exerts broad-spectrum, high-potency activity against both influenza A and B viruses, maintains immune effector function, and provides prolonged exposure. Compared with first-generation ADFC molecules, AK0406 is engineered to offer an optimized profile for both prophylaxis and treatment of influenza infection. The phase I trial is a single-center, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and pharmacokinetic (PK) profile of AK0406 in healthy adult participants in Australia. Data from this FIH study will inform subsequent dose selection and future proof-of-concept trials in populations at risk for influenza infection. Influenza remains a significant global public health burden, causing substantial morbidity and mortality each year and posing an ongoing pandemic threat. Current preventive measures, including seasonal vaccination, are challenged by antigenic drift, strain-selection uncertainty, and reduced effectiveness in the general population, especially in vulnerable groups such as older adults and immunocompromised individuals. With its long-acting, broad-spectrum ADFC design, AK0406 has the potential to address key limitations of existing therapies and offer improved options for both prevention and treatment of seasonal influenza and potential pandemic outbreaks. ArkBio will continue to accelerate the clinical development of AK0406 and work with global partners to advance better prevention and treatment options for patients worldwide. About ArkBio ArkBio is a commercial-stage biotechnology company focused on the discovery and development of innovative therapeutics for respiratory/lung and pediatric diseases. Founded in 2014, the company has established proprietary technology platforms and a differentiated R&D pipeline through internal innovation and strategic collaborations. Key pipeline assets include: ziresovir (AK0529), the first direct-acting antiviral for RSV with positive pivotal phase 3 results; AK3280, a potentially best-in-class anti-fibrotic agent with positive phase 2 results in idiopathic pulmonary fibrosis and is advancing into Phase 3 registrational trials; AK0901, approved and commercialized in China for the treatment of ADHD. The company also has multiple first-in-class or best-in-class innovative candidates in clinical or preclinical development. ArkBio has established strategic partnerships with multinational pharmaceutical companies including Roche and Genentech, leading academic institutions such as The Scripps Research Institute and the Institute of Microbiology of the Chinese Academy of Sciences, Qilu Pharmaceutical as well as other domestic and international biotech companies and CROs. For more information, please visit: Investor Inquiries: [email protected] SOURCE Arkbio 21% more press release views with Request a Demo

Hepatocytes have wide applications in drug development, disease modeling, and cell therapy. However, expanding hepatocytes in large quantities in vitro without compromising their functions remains a significant challenge. Previously, a few studies have demonstrated that chemical cocktails with growth factors or cytokines can support mouse and human hepatocyte expansion in vitro. However, the culture conditions are complex, and long-term cultivation often leads to hepatocyte functional decline. Due to the wide application of primary hepatocytes, developing simple and efficient ways to expand hepatocytes in vitro is an important and meaningful task. In a study published in the Journal of Hepatology, a team of scientists led by XIE Xin from the Shanghai Institute of Materia Medica, the Chinese Academy of Sciences (CAS), discovered that the cytokine IL-22 supports long-term expansion of mouse and human hepatocytes in vitro. Previously, they reported a simple culture condition containing IL-6 can support the long-term in vitro expansion and functional maintenance of mouse primary hepatocytes. The scientists discovered that the cytokine IL-22 was dramatically upregulated in the plasma of mice following 70%-PHx (partial hepatectomy) and after hepatocyte transplantation in Fah-/- mice. When culturing mouse primary hepatocytes in the classical hepatocyte culture medium supplemented with IL-22, the hepatocytes expand for more than 30 passages, reaching a theoretical expansion of more than 1030-fold over 150 days (Figure 1). The IL-22 containing medium supports the growth of primary hepatocytes by dedifferentiating the cells into induced hepatocyte progenitor cells (IL-22-iHPCs), which maintain the capacity of differentiation into functionally mature hepatocytes (IL-22-iMHs). The function and therapeutic potential of IL-22-iMHs were further investigated in vivo. After transplantation IL-22-iMHs into Fah-/- mice, IL-22-iMHs significantly improved the survival rate of Fah-/- mice and repopulate 90% of the liver of Fah-/- mice in 2 months (Figure 1). Further research demonstrated that IL-22 induces hepatocyte proliferation by activating the Stat3 signaling pathway and the downstream key transcription factors Bhlha15 and Arntl2. Knockout of Stat3 completely blocks IL-22 induced hepatocyte proliferation. Expressing the transcription factors Bhlha15 and Arntl2 in hepatocytes can induce hepatocyte to dedifferentiate into expandable iHPCs (Figure 1). Figure 1: IL-22 induces long-term expansion of mouse hepatocytes via the Stat3-Bhlha15/Arntl2 pathway IL-22 could also induce human primary hepatocyte to dedifferentiate into hepatocyte progenitor cells (IL-22 induced human hepatocyte progenitor cells, IL-22-hiHPCs). Expansion of a single IL-22-hiHPC could be captured when passaged at very low density, and a single IL-22-hiHPC at early passages could give rise to 600 cells in 7 days. IL-22-hiHPCs could be passaged at least 5 times, with the cumulative cell number increasing 103-104 fold in ~30 days depending on the donors. Hepatocytes from the two younger donors aged <30 years exhibited higher expansion capability and expanded for more than 6×104 fold in 30 days. IL-22-hiHPCs could re-differentiate into mature hepatocytes (IL-22 induced human mature hepatocytes, IL-22-hiMHs), IL-22-hiMHs highly expressed the hepatic markers such as AAT and CYP7A1 (Figure 2). Upon transplantation IL-22-hiMHs into immunodeficient Fah⁻/⁻ mice (NPG-Fah-/- mice), IL-22-hiMHs significantly improved the survival rate of NPG-Fah-/- mice and repopulated more than 30% of the liver of NPG-Fah-/- mice in 2 months (Figure 2). Figure 2: IL-22 supports in vitro proliferation and functional maintenance of human primary hepatocytes This study established a novel method for expanding mouse and human hepatocytes in vitro. The underlying mechanism involves the activation of Stat3 pathway and upregulation of two downstream TFs, Bhlha15 and Arntl2, which govern hepatocyte dedifferentiation and proliferation. This physiological and simple way to expand primary hepatocytes in vitro may provide new insights into culturing previously difficult-to-culture cell types and support their application in regenerative medicine. Figure 3: Graphical Abstract (Image by XIE Xin’s lab) Link: https://www.sciencedirect.com/science/article/pii/S0168827826000565?via%3Dihub Contact: DIAO Wentong Shanghai Institute of Materia Medica E-mail: diaowentong@simm.ac.cn