"MeiraGTx, Touchlight Genetics and Symbiosis Pharmaceutical Services are collaborating to develop an improved Adeno-associated virus manufacturing process. The process will be improved through a number of different routes to deliver a cost effective large-scale bioreactor manufacturing process for the production of AAV gene therapies Through our collaborative bioreactor development program we will achieve: * An increased yield of infectious AAV particles sufficient to enable the transition of gene therapies from niche to more first line therapy and higher dose indications * A serum free process -- reducing regulatory risk, adventitious agent testing costs, and a source of variability * A synthetic DNA transduction method -- removes common blockages in the manufacturing supply chain, reduces COGs, reducing regulatory risk, reduction in adventitious agent testing costs, and a source of variability * A lower cost of goods due to improved process efficiency, represented by a higher product output from the same GMP suite time"

Six recombinant adeno-associated virus (rAAV) gene therapies have been commercially approved with a growing pipeline of \>550 under development globally. However, they exhibit prohibitive pricing and a long and expensive journey into the clinic partly due to inefficient manufacturing processes. Wider patient access requires increased productivity and efficiency to lower cost-of-goods (COGS), improving affordability to the NHS and healthcare organisations. CGT Catapult is a not-for-profit UK research and technology organisation committed to the advancement of ATMPs and enhancement of the UK industry. CGT Catapult has developed a scalable process and analytical platform for rAAV manufacture and, aligned with its remit to support industry growth, has transferred this platform to leading industry partners and Contract Development Manufacturing Organisations (CDMOs). Touchlight has developed an innovative enzymatic DNA manufacturing platform and GMP production capability which offers the speed, scale and purity to support rapid growth of genetic medicines, substituting plasmid DNA (pDNA) in rAAV production by their proprietary dbDNA. This project aims to combined both assets by the use of dbDNA as a starting material in the CGT Catapult's rAAV manufacturing platform which will enable a more streamlined path to clinical rAAV supply for the UK biotech sector than the current industry standard, pDNA. This will help reduce cost of goods and timelines to access GMP DNA, through utilisation of Touchlight's manufacturing process, and the dissemination and transfer of this dbDNA-based platform to the rAAV industry enabling other UK manufacturing partners to establish their own dbDNA-based manufacturing process thereby improving the successful translation of emerging rAAV based nucleic acid therapeutics from academia to industry. The clinical relevance of this platform will be proven through the supply and use of the Complement Therapeutics rAAV product genome sequence, in connection with the proprietary therapeutic product currently being developed by Complement Therapeutics, in the conduct of the Project by Touchlight, benefiting from accessing this optimised platform through their established relationship with CGT Catapult while reducing their costs and timelines in their journey into the clinic through the use of Touchlight's dbDNA. Touchlight will further characterise rAAV9 production from dbDNA using a new RepCap dbDNA construct. This project will deliver against the UK government's Life Sciences Vision, creating a globally competitive biomanufacturing infrastructure and further establishing the UK's precedence as a leader in innovation, manufacturing and regulation of advanced therapies. This will certainly enable the Next Generation of UK-based Advanced Therapies Innovators and have a big impact in improving rAAV therapies accessibility and affordability bringing them closer to the patients.

Recent advancements in non-viral gene editing technologies offer precise genome engineering at significantly reduced costs and biosafety risks compared to viruses. CRISPR is a programmable genome targeting system, using DNA as a template for homology-directed repair (HDR) to introduce exogenous sequences for cell and gene therapy. ssDNA is more efficient, less toxic and more specific than double-stranded DNA (dsDNA) when used as HDR template for gene editing. However, due to difficulties in its manufacture, GMP lssDNA at scale is still unavailable, forcing non-viral gene editing to largely rely on plasmid DNA as donor for gene-length insertions, despite the high immunogenicity, low knock-in efficiencies and off-target effects associated with it. In response to the growing need for reliable and effective vectors for targeted gene insertions, Touchlight has developed a platform, producing a novel lssDNA, MegaBulb DNA (mbDNATM), which overcomes the size limitations and manufacturing scalability bottlenecks of existing lssDNA and viruses. mbDNA is a closed single-stranded fully synthetic CRISPR gene editing template comprising a short complementary stem region with a target site for a guided endonuclease. Extensive evaluations have shown that mbDNA exhibits extremely low toxicities and outperforms dsDNA and open lssDNA as a CRISPR HDR template in primary cells. Importantly, unlike other lssDNA manufacture platforms, mbDNA's production relies on Touchlight's well established, rapidly scalable, quick turnaround technology -- doggybone DNA (dbDNATM). By leveraging Touchlight's CDMO facilities and technical capabilities, the mbDNA platform promises to be significantly more efficient and affordable, allowing production of lssDNA at the multi-milligram scales required by the gene editing market for the first time. This will facilitate access to lssDNA and advance gene therapies making them better, safer and cheaper, allowing to tackle unmet clinical needs. Through mbDNA commercialisation, this work will enable seminal advances in gene therapy. To achieve this, we will extensively characterise mbDNA, develop relevant analytical methods and scale up its manufacture. Molecular characterisation will facilitate mbDNA's functional understanding, inform and improve production pipelines and quality control development of the novel GMP-compatible process, thus facilitating commercialisation. Through this collaborative work we aim to establish and develop innovative analytical methods to enable mbDNA process development and scale up to supply it as a vital ingredient for the gene editing industry. Taking mbDNA to market will make it available for use by the industry in cell and gene therapy pipelines, where with its improved gene editing profile mbDNA commercial availability promises to revolutionise the field.

Toxic medicines are becoming a major focus of the pharmaceutical industry, as high potency products need minimal amounts to dose patients and so material requirements are low. However, the associated risks of working with these toxic products can make their development problematic, and traditional manufacturing routes are often unsuitable. This project will examine using cell free expression to produce a botulinum toxin from a "doggybone DNA" (dbDNA) vector. The project will develop a closed loop system for producing dbDNA, and screen a wide range of conditions to optimise a cell free expression system, for enclosed processing of toxins to negate the health and safety risks and technical yield limitations associated with high potency biopharmaceutical production. The project is a collaboration led by Ipsen Biopharm, involving Touchlight Genetics and the Centre for Process Innovation.

Nanowires are simply very thin wires, but they have unusual and useful properties because of their size (1000x thinner than hair).In particular, the flow of small electric currents in a nanowire responds to the presence of chemicals, and quantum confinement allows for controllable photoluminescent properties.Many gases of relevance to industrial processes, or healthcare (compounds in breath), or environmental pollutants (oxides of nitrogen, ozone) can be sensed using nanowire-based devices.Quantum dots can be used for a number of applications, such as optical barcodes and display screens.However, a number of manufacturing and technical obstacles remain. Methods for preparing semiconductor nanowires exist, but these require elaborate equipment and high expense.Work at Newcastle University has shown that nanowires may be formed by low temperature reactions in water using DNA as a template on which to form the semiconductor as a nanowire. Until the recent advances by Touchlight Genetics, large quantities of pure, synthetic DNA were not available.The collaboration between Touchlight and Newcastle will aim to develop manufacturing techniques to exploit the novel possibilities for sensor manufacture that these advances enable.

Gene therapy is becoming an increasingly important method of treatment for a variety of major unmet medical needs especially in the areas of inherited and rare diseases and diseases of the eye, conditions which are life threatening or significantly diminish quality of life. Adeno-associated virus (AAV) vectors are currently the delivery vehicle of choice for gene therapy treatments but the advancement these treatments into clinical trials is currently hampered by the time and expense required to manufacture these vectors. The proposed collaboration between Cobra and Touchlight will develop a fast and less expensive route to manufacture of AAV vectors, which will enable the acceleration of more potential products into clinical testing. This in turn will increase the chances of treatment being developed for a whole range of these currently intractable diseases.

The collaboration between Synpromics Ltd. and Touchlight Genetics Ltd. will combine two highly innovative and complementary technology platforms to develop an improved approach to developing DNA vaccines. The project will leverage Synpromics's proprietary technology to rationally design synthetic promoters that drive cell-specific antigen expression and that enhance the effectiveness of Touchlight Genetics’s unique synthetic DNA vaccine cassette platform. The resulting new technology will subsequently be applied by Touchlight Genetics in the company’s internal DNA vaccine develoment programs, as well as be available for licensing by other developers. The project is expected to establish a unique UK-based synthetic biology capability for the production of safer and more effective DNA-based medicines.

To develop the cloning and expression of DNA metabolising enzymes to enhance the biosynthesis of novel DNA vaccine constructs devoid of contaminating bacterial DNA sequences.