Vilnius University

Scientists have developed a new method to measure the smallest twists and torques of molecules within milliseconds. The method makes it possible to track the gene recognition of CRISPR-Cas protein complexes, also known as 'genetic scissors', in real time and with the highest resolution. With the data obtained, the recognition process can be accurately characterized and modeled to improve the precision of the genetic scissors. When bacteria are attacked by a virus, they can defend themselves with a mechanism that fends off the genetic material introduced by the intruder. The key is CRISPR-Cas protein complexes. It is only in the last decade that their function for adaptive immunity in microorganisms has been discovered and elucidated. With the help of an embedded RNA, the CRISPR complexes recognise a short sequence in the attacker's DNA. The mechanism of sequence recognition by RNA has since been used to selectively switch off and modify genes in any organism. This discovery revolutionised genetic engineering and was already honoured in 2020 with the Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer A. Doudna. Occasionally, however, CRISPR complexes also react to gene segments that differ slightly from the sequence specified by the RNA. This leads to undesirable side effects in medical applications. "The causes of this are not yet well understood, as the process could not be observed directly until now," says Dominik Kauert, who worked on the project as a PhD student. Nanoscale processes tracked in detail To better understand the recognition process, the team led by Professor Ralf Seidel and Dominik Kauert took advantage of the fact that the DNA double helix of the target sequence is unwound during recognition to enable base pairing with the RNA. "The central question of the project was therefore whether the unwinding of a piece of DNA that is only 10 nanometres (nm) long could be tracked in real time at all," says Kauert. To observe the unwinding process in detail, the scientists had to make it visible to the microscope. To achieve this goal, the team drew on the achievements of DNA nanotechnology, which can be used to create any three-dimensional DNA nanostructure. Using this so-called DNA origami technique, the researchers constructed a 75 nm long DNA rotor arm with a gold nanoparticle attached to its end. In the experiment, the unwinding of the 2 nm thin and 10 nm long DNA sequence was transferred to the rotation of the gold nanoparticle along a circle with a diameter of 160 nm -- this movement can be magnified and tracked using a special microscope setup. With this new method, the researchers were able to observe the sequence recognition by the CRISPR Cascade complex almost base pair by base pair. Surprisingly, base pairing with the RNA is not energetically advantageous, meaning that the complex is only unstably bound during sequence recognition. Only when the entire sequence is recognised does stable binding occur and the DNA is subsequently destroyed. If it is the "wrong" target sequence, the process is aborted. Findings will help in selecting suitable RNA sequences The fact that the recognition process sometimes produces incorrect results is due to its stochastic nature, i.e. to random molecular movements, as the researchers have now been able to demonstrate. "Sequence recognition is driven by thermal fluctuations in base pairing," says Kauert. With the data obtained, it was possible to create a thermodynamic model of sequence recognition that describes the recognition of deviating sequence segments. In the future, this should allow better selection of RNA sequences that recognise only the desired target sequence, thus optimising the precision of genetic manipulation. As the designed nanorotors are universal in their suitability for measuring twists and torques in single molecules, they can also be used for other CRISPR-Cas complexes or biomolecules. The work was funded by the European Research Council and the German Research Foundation and carried out in collaboration with the research group of Professor Virginijus Siksnys from Vilnius University in Lithuania, who isolated and provided the CRISPR complexes used.

$4.8 million funding from Vsquared Ventures, Practica Capital and Metaplanet, bringing total funding to over $8 million New capital will support a worldwide commercial organisation, enabling a direct U.S. presence Launch of new semi-permeable capsule technology to unlock breakthroughs in scientific discovery and innovation VILNIUS, Lithuania & DENVER--(BUSINESS WIRE)-- Backed by international investors, Atrandi Biosciences is establishing a direct team to support customers in the U.S. and advancing the global commercialization of its breakthrough microfluidic and single-cell analysis technologies. This press release features multimedia. View the full release here: Atrandi Biosciences is empowering discoveries by providing powerful and accessible molecular analysis tools that allow scientists to explore a single cell with unprecedented precision and depth. (Photo: Business Wire) Following a $4.8 million funding round led by Vsquared Ventures and completed by Practica Capital and Metaplanet, the microfluidics specialist will provide researchers around the world with the tools and support to accelerate scientific discovery and innovation, from individualised treatment for cancer patients to new and effective therapies for a wide range of other diseases. "Over twenty years after the human genome was sequenced, science still lacks a fundamental understanding of biology. The main barrier has been the lack of high-throughput, viable technology to culture, manipulate and rigorously analyse biological samples at the level of individual cells," said Juozas Nainys, PhD, Chief Executive Officer of Atrandi Biosciences. "With our new semi-permeable capsule technology, we overcome these limitations and give scientists the tools necessary to fully unleash the potential of single-cell experiments, next-generation genome sequencing, AI-driven drug discovery or personalised medicine." Innovations in microfluidics have enabled the study of blood, tumors, pathogens, engineered cell lines, and other samples at individual cell resolution. However, these studies lack the necessary biological information content and scale to fully realise the benefits. The limitations of conventional microfluidic technologies include high cost, limited applicability to different workflow types, and a limited number of single-cell data points analysed. With its proprietary semi-permeable capsule technology, Atrandi delivers a next-generation platform that overcomes all these bottlenecks. By delivering efficient and reliable molecular analysis tools, embracing an open-source approach to assay designs and consumables, and providing world-class scientific support, the Atrandi team is therefore empowering researchers to drastically improve their single-cell and single-molecule workflows. Disrupting a multi-billion dollar market from Lithuania "Atrandi's breakthrough technology will not only disrupt the existing multibillion-dollar liquid handling market, but open up entirely new applications, from personalised oncology to cell-therapy research," said Lise Rechsteiner, General Partner of Vsquared Ventures. "In doing so, Atrandi can build on its well-oiled commercial business and the decades of experience of a team of top scientists. We are excited to support the innovators at Atrandi in the next phase of their evolution as they expand their global presence into the U.S.'' Founded in 2016 by Harvard-trained pioneers in single-cell genomics under the former name Droplet Genomics, Atrandi has its global headquarters in Vilnius, Lithuania, the home country of its founders and an emerging deep tech hub. The company is firmly rooted in the local ecosystem of innovative start-ups, established biotech corporations, renowned universities and research institutions and already supplies international customers with its high-throughput screening platform Styx and its droplet generator Onyx. "Usually, top researchers trained at European universities leave Europe to start companies in the United States. In Atrandi's case, it was the other way around. The team were trained at the best U.S. universities before deciding to start their business out of Vilnius," says Donatas Keras, Partner at Practica Capital. "This shows how attractive the Lithuanian and European ecosystem has become for entrepreneurs who want to build a global player. It is a testament to the talent and potential of our local ecosystem. Being the first investors in the company and partnering early with such a talented team with roots in our country is a source of immense pride. We look forward to their continued success solving some of the world's most pressing health challenges." Given the significant improvements over conventional technology and the versatility of its new semi-permeable capsule technology, Atrandi intends to massively strengthen its market position. “The upcoming launch of our semi-permeable capsule technology offers a unique opportunity for Atrandi to become synonymous with microfluidics,” said Juozas Nainys. “In Lithuanian, Atrandi means ‘you discover’. And at Atrandi, we are dedicated to advancing scientific discovery and innovation by delivering state-of-the-art technologies and services that unlock the full potential of single-cell genomics. With a steadfast commitment to excellence, integrity, and innovation, we strive to be a trusted partner and ally for scientists around the world as they work to unravel the mysteries of biology.” About Atrandi Biosciences Atrandi Biosciences ( ) is an emerging developer and provider of innovative microfluidic solutions for the life sciences. Its novel technology platform enables new insights into the biology of single cells, with immediate applications in research and bio-molecular discovery. Atrandi’s systems are installed in over 50 leading academic and commercial laboratories globally with a rapid growth trajectory. View source version on businesswire.com: Contacts Juozas Nainys, CEO: juozas.nainys@atrandi.com Andy Watson, Board Chair: andy.watson@atrandi.com Julie Ferguson, CG Life: jferguson@cglife.com Source: Atrandi Biosciences Smart Multimedia Gallery Photo Atrandi Biosciences is empowering discoveries by providing powerful and accessible molecular analysis tools that allow scientists to explore a single cell with unprecedented precision and depth. (Photo: Business Wire) Photo Born in 2016, from their foundational research in the labs of Harvard University, Columbia University, Oxford University, and Vilnius University, the founders were inspired to design solutions to address the lack of flexibility offered by existing R&D platforms that had hindered their own experiments. Today, Atrandi is home to life science, engineering, and chemistry experts that have pushed the boundaries of current liquid handling processes. (Photo: Business Wire) Logo View this news release and multimedia online at:

SAN DIEGO--(BUSINESS WIRE)-- ADARx Pharmaceuticals, Inc., a biotechnology company developing RNA-targeting therapeutics, today announced the further expansion of their leadership team and clinical development capabilities through the appointment of Feriandas Greblikas, M.D. as Vice President of Clinical Development. “We are very excited to have Feriandas join the ADARx team,” said Dr. Zhen Li, President and Chief Executive officer of ADARx. “With his wealth of experience in drug development and clinical execution, he will make significant contributions to ADARx’s strategy, and operational effectiveness as we continue to advance programs to the clinic.” Dr. Greblikas joins ADARx as ADX-324 for the treatment of hereditary angioedema is set to start phase I clinical trials later this year and two additional drug candidates are expected to enter clinical trials next year. Dr. Greblikas is an established physician-scientist with more than 10 years of extensive experience in drug development, medical oversight, clinical trial planning and execution. Prior to joining ADARx, Dr. Greblikas served as a Senior Medical Director at Travere Therapeutics, in which he contributed to the development of pegtibatinase and fosmetpantothenate programs. Prior positions include Medical Director at BioMarin, Baxter and Biogen, and significant contributions to approved drugs Palynziq®, Adynovate® and Eloctate®. Dr. Greblikas received his M.D. in pediatrics from the Vilnius University. Dr. Greblikas also holds an Economics diploma from the International Business School of Vilnius University. “I am delighted to join the passionate team at ADARx and be part of a shared commitment of bringing safe and effective treatments to patients with unmet needs,” said Dr. Greblikas. “The ADARx pipeline presents diverse options for first-in-class and best-in-class drugs to realize this commitment.” About ADARx ADARx Pharmaceuticals, Inc., located in San Diego, is a biotechnology company committed to turning cutting-edge science into life-saving therapeutics. ADARx is developing a proprietary RNA targeting platform, including oligonucleotides for inhibition, degradation, and editing, together with novel oligonucleotide delivery technologies. ADARx has a growing pipeline of RNA targeting therapeutics for treating diseases across a range of therapeutic areas including genetic, cardiometabolic, complement-mediated and central nervous system diseases. ADARx lead programs are entering clinical stage.