Fangtuo Biotechnology (Suzhou) Co., Ltd.

Scientists have created a working nanoscale electomotor. The science team designed a turbine engineered from DNA that is powered by hydrodynamic flow inside a nanopore, a nanometer-sized hole in a membrane of solid-state silicon nitride. The tiny motor could help spark research into future applications such as building molecular factories or even medical probes of molecules inside the bloodstream. Scientists have created the world's first working nanoscale electromotor, according to research published in the journal Nature Nanotechnology. The science team designed a turbine engineered from DNA that is powered by hydrodynamic flow inside a nanopore, a nanometer-sized hole in a membrane of solid-state silicon nitride. The tiny motor could help spark research into future applications such as building molecular factories for useful chemicals or medical probes of molecules inside the bloodstream to detect diseases such as cancer. "Common macroscopic machines become inefficient at the nanoscale," said study co-author professor Aleksei Aksimentiev, a professor of physics at the University of Illinois at Urbana-Champagne. "We have to develop new principles and physical mechanisms to realize electromotors at the very, very small scales." The experimental work on the tiny motor was conducted by Cees Dekker of the Delft University of Technology and Hendrik Dietz of the Technical University of Munich. Dietz is a world expert in DNA origami. His lab manipulated DNA molecules to make the tiny motor's turbine, which consisted of 30 double-stranded DNA helices engineered into an axle and three blades of about 72 base pair length. Decker's lab work demonstrated that the turbine can indeed rotate by applying an electric field. Aksimentiev's lab carried out all-atom molecular dynamics simulations on a system of five million atoms to characterize the physical phenomena of how the motor works. The system was the smallest representation that could yield meaningful results about the experiment; however, "it was one of the largest ever simulated from the DNA origami perspective," Aksimentiev said. Mission Impossible to Mission Possible The Texas Advanced Computing Center (TACC) awarded Aksimentiev a Leadership Resource Allocation to aid his study of mesoscale biological systems on the National Science Foundation (NSF)-funded Frontera, the top academic supercomputer in the U.S. "Frontera was instrumental in this DNA nanoturbine work," Aksimentiev said. "We obtained microsecond simulation trajectories in two to three weeks instead of waiting for a year or more on smaller computing systems. The big simulations were done on Frontera using about a quarter of the machine -- over 2,000 nodes," Aksimentiev said. "However, it's not just the hardware, but also the interaction with TACC staff. It's extremely important to make the best use of the resources once we have the opportunity." Aksimentiev was also awarded supercomputer allocations for this work by the NSF-funded Advanced Cyberinfrastructure Coordination Ecosystem: Services & Support (ACCESS) on Expanse of the San Diego Supercomputer Center and Anvil of Purdue University. "We had up to 100 different nanomotor systems to simulate. We had to run them for different conditions and in a speedy manner, which the ACCESS supercomputers assisted with perfectly," Aksimentiev said. "Many thanks to the NSF for their support -- we would not be able to do the science that we do without these systems." DNA as a Building Block The success with the working DNA nanoturbine builds on a previous study that also used Frontera and ACCESS supercomputers. The study showed that a single DNA helix is the tiniest electromotor that one can build -- it can rotate up to a billion revolutions per minute. DNA has emerged as a building material at the nanoscale, according to Aksimentiev. "The way DNA base pair is a very powerful programming tool. We can program geometrical, three-dimensional objects from DNA using the Cadnano software just by programming the sequence of letters that make up the rungs of the double helix," he explained. Another reason for using DNA as the building block is that it carries a negative charge, an essential characteristic to make the electromotor. "We wanted to reproduce one of the most spectacular biological machines -- ATP synthase, which is driven by electric field. We chose to do our motor with DNA," Aksimentiev said. "This new work is the first nanoscale motor where we can control the rotational speed and direction," he added. It's done by adjusting the electric field across the solid state nanopore membrane and the salt concentrations of the fluid that surrounds the rotor. "In the future, we might be able to synthetize a molecule using the new nanoscale electromotor, or we can use it to as an element of a bigger molecular factory, where things are moved around. Or we could imagine it as a vehicle for soft propulsion, where synthetic systems can go into a blood stream and probe molecules or cells one at a time," Aksimentiev said. If you think this sounds like something out of a 1960's sci-fi movie, you are right. In the movie Fantastic Voyage, a team of Americans in a nuclear submarine is shrunk and injected into a scientist's body to fix a blood clot and need to work quickly before the miniaturization wears off. As far-fetched as this might sound, Aksimentiev says that the concept and the elements of the machines we are developing today could enable something like this to happen. "We were able to accomplish this because of supercomputers," Aksimentiev said. "Supercomputers are becoming more and more indispensable as the complexity of the systems that we build increases. They're the computational microscopes, which at ultimate resolutions can see the motion of individual atoms and how that is coupled to a bigger system." Funding came from ERC Advanced Grant no. 883684 and the NanoFront and BaSyC programmes; ERC Consolidator Grant to H.D. (GA no. 724261), the Deutsche Forschungsgemeinschaft via the Gottfried-Wilhelm-Leibniz Programme (to H.D.) and the SFB863 Project ID 111166240 TPA9; National Science Foundation grant DMR-1827346; the Max Planck School Matter to Life and the MaxSynBio Consortium. Supercomputer time was provided through TACC Leadership Resource Allocation MCB20012 on Frontera and through ACCESS allocation MCA05S028.

In a Series B funding round supported by Boyu Capital, Sequoia China, OrbiMed and Creacion Ventures, among others, Frontera Therapeutics closed on a Series B funding round worth $160 million Wednesday. Headquartered in Bedford, Massachusetts and Suzhou, China, Frontera focuses on gene therapies. Its novel APEX Technology & Manufacturing platform is an adeno-associated virus (AAV) gene expression system designed to optimize new and clinically validated AAV vectors for improved safety and efficacy. The company also has in-house GMP manufacturing capabilities. In addition to the Series B round, the company announced that the U.S. Food and Drug Administration had accepted its Investigational New Drug application to launch a first-in-human clinical study of FT-001. The gene therapy candidate is being developed for patients with Leber congenital amaurosis (LCA), a rare genetic retinal disease that causes severe loss of vision, “FT-001’s IND clearance by the FDA is an exciting operational accomplishment for the Frontera scientific and management teams,” Wei Li, Ph.D., chairman and founding partner of Creacion Ventures said. “Its potential success in the clinic would be an important step toward validating the broader APEX Technology & Manufacturing platform. By creating the first fully-integrated, efficient and scalable adeno-associated virus (AAV) gene expression system, Frontera has the opportunity to shorten the time between product discovery, clinical development and ultimately approvals across multiple programs.” Frontera Hopes to Have 4 Clinical-Stage Drugs in 2023 To date, the company has raised $195 million since its founding in 2019. The initial Series A brought in $35 million from OrbiMed and Creacion. The company is planning clinical trials in both the U.S. and China. Stephen Lau, the company’s chief business officer told the Boston Business Journal it is considering a potential crossover financing round and at the same time, hopes to enter the clinic with four new drugs in the next year. The focus of the gene therapies is on orphan diseases, which typically affect fewer than 200,000 people globally. They may also focus on rare disease that affect more people. “In less than two years, we’ve gone from a paper-napkin concept to an open IND in the U.S., with full clinical material ready for enrollment later this year,” Lau said. “The speed of execution is quite extraordinary. We’ll have three other programs coming in around the same timeline.” Lau describes the company’s strategy as a multistep process starting with choosing the right disease to treat. LCA is an interesting example because it is a clinically validated target, but there’s also already a gene therapy on the market, Spark Therapeutics’ Luxturna. In fact, Luxturna was the first gene therapy to ever be approved by the FDA. Secondly, Frontera is building out its manufacturing capabilities. The third step is to scale the drug development and manufacturing processes at the same time. The company may also launch clinical trials first in China, where the process is more straightforward than in the U.S. However, the FDA has recently been showing resistance to approving drugs based only on clinical studies performed in China. That’s not uncommon for other countries, either. Japan, for example, typically requires some studies to be conducted in Japan to ensure there are no race-specific discrepancies in drug effects. Lau believes that this approach would allow the company to choose whether to continue clinical studies in China or the U.S. “Once you see a half-dozen or a dozen patients, you know the dosing and safety and protein expression profile. That’s really the litmus test, the human data," he said. The $160 million raised should give the company “a couple of years” runway, according to Lau, although he’s already discussing a potential crossover round with investors. An initial public offering (IPO) could also occur in the next few years. The company currently staffs more than 100 people, with slightly under half in Massachusetts. It is currently hiring. “We are very pleased by the strong support from leading international investment firms in the completion of this financing round as we strive to create value for both patients and shareholders,” Yong Dai, Ph.D., founder and chief executive officer of Frontera stated. “The recent clearance of the IND for FT-001 by the FDA, which took less than two years to accomplish from program inception, is a testament to our execution capabilities.”

Auron Scores $48M to Identify AI-Based Cancer Targets Frontera Scoops Up $160M for AAV Gene Therapy Tech & Manufacturing Medical Microinstruments Scores $75M for Robotic Microsurgery OSE Raises Another $300 M for University of Oxford Startups Immunocore Raises $140M to Fuel Oncology & Infectious Disease Pipeline Money came from a variety of sources this week. Binding letters of intent, private placement financing, rights offerings and regular VC funding rounds are paving the way for gene therapy manufacturing, melanoma treatments, robotic microsurgery and long-haul COVID therapy. Auron Scores $48M to Identify AI-Based Cancer Targets Massachusetts-based Auron Therapeutics is starting off strong with $48 million in Series A financing. The biopharmaceutical company targets dysregulated differentiation and cellular plasticity for treating cancer. The funding will help Auron advance its most unique aspect: a machine-learning computational platform that identifies novel drug targets. By targeting cellular plasticity, the platform is designed to identify differentiation pathways that have been taken over by cancer cells. Rather than attacking tumor cells like traditional cancer treatment methods, Auron’s approach drugs the hijacked pathways to stop cancer cells from proliferating. Auron’s plan is to bring newly discovered drugs to the clinical stage, either as monotherapies or combination therapies. “The novel targets identified using Auron’s platform may enable completely innovative approaches to treating cancer that are complementary, rather than competitive, with existing therapeutics,” Briggs Morrison, M.D., independent chairman of the board said. Frontera Scoops Up $160M for AAV Gene Therapy Tech & Manufacturing Gene therapy company Frontera Therapeutics dominated its Series B funding round with $160 million, thanks to investors such as Boyu Capital, Sequoia China, OrbiMed and Creacion Ventures. The massive cash infusion came with a second exciting announcement: the U.S. Food and Drug Administration accepted Frontera’s Investigational New Drug application to start a first-in-human clinical trial for FT-001, a gene therapy to treat a rare genetic retinal disease that causes vision loss. In addition to supporting FT-001, the money will advance Frontera’s APEX technology & manufacturing platform. The platform is an adeno-associated virus (AAV) gene expression system that makes gene therapy development more efficient and expands gene therapies to new areas of treatment, such as ophthalmology, hematology, neurology and metabolic diseases. Medical Microinstruments Scores $75M for Robotic Microsurgery Italy-based Medical Microinstruments S.r.l. Inc. (MMI)’s Series B financing was a success, raising $75 million. The cash will help advance its robotic microsurgery mission of performing surgery in veins, arteries, nerves and lymphatic vessels as small as 0.3 mm in diameter. The first priority for the $75 million will be to continue commercialization efforts for MMI’s proprietary Symani Surgical System in Europe, where it received CE mark in 2019. The Series B cash will also help MMI expand into the U.S. and Asia-Pacific areas. The company hopes to conduct a pivotal study with its machinery and is aiming for an Investigational Device Exemption from the FDA. OSE Raises Another $300 M for University of Oxford Startups Oxford Science Enterprises (OSE), an independent company that partners with the University of Oxford to fund potential businesses, raised £250 million (approximately €294 million/USD$300 million) on Monday. The money came from an array of international investors and brings OSE’s total funding to about £850 million (€1 billion/USD$1.02 billion). The new funds will support OSE’s portfolio of around 40 businesses. As these businesses mature, the company will offer larger amounts of money to later-stage businesses in life sciences, health tech and deep tech. So far, OSE has supported more than 80 companies, taking two of them to IPO and drawing more than £1B from other global investors. In April, OSE joined Sanofi Ventures and GV in supporting OMass Therapeutics with a $100 million Series B financing. “Our companies are making remarkable breakthroughs from cancer, heart failure and infectious diseases to climate change, food security and quantum computing. Over the next few years, we expect these companies will continue to make important progress; with our ongoing efforts and the support of our shareholders, we look forward to helping them deliver impact and returns,” OSE CEO Alexis Dormandy said. Immunocore Raises $140M to Fuel Oncology & Infectious Disease Pipeline Commercial-stage biotech company Immunocore announced a private placement financing on Monday. In the transaction, Immunocore sold around 3.7 million shares to private investors, raising about $140 million in capital. Immunocore already has plans for the money. The cash will fuel its oncology and infectious disease treatment pipelines, including advanced cutaneous melanoma drug tebentafusp and assets targeting MAGE-A4 and PRAME, genes which, when overexpressed, are associated with cancer. The sizeable private placement, in conjunction with expected profits from KIMMTRAK, a treatment for metastatic uveal melanoma, is expected to be sufficient to fund Immunocore’s operating plan through 2025.