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80 SYNTHETIC BIOLOGY


genetic modifications. Unlike conventional genetic engineering (which requires the introduction of DNA from other species), gene editing allows modifications such as additions, removals, or cuts to be made at specific locations in the genome. What is more, because gene editing


does not introduce foreign DNA, organisms modified in this way do not have to be labelled as genetically modified (GMO) in some jurisdictions. This can be advantageous when it comes to gaining consumer acceptance for the products they are used in. It is also worth noting that provisions in Directive 2001/18/EC on the deliberate release into the environment of GMOs do not apply to the cosmetic ingredients produced by GMOs. Of the available gene editing techniques,


CRISPR-Cas9 is considered the easiest, simplest, cheapest, and most efficient. Some genomics experts believe it will revolutionise how the personal care industry sources ingredients. In fact, CRISPR-Cas9 is already being used to modify terpenoid synthesis pathways in microbes to bring about overproduction of squalene.3 Several biotech companies have also used


advances in CRISPR to successfully generate a microbial palm oil alternative using various strains of yeast. Meanwhile, Swiss biotech company Evolva employs the technique to develop nature-based flavours, fragrances, and other cosmetics ingredients.3 In a similar vein, biotech firm Amyris


has used genetic engineering to transfer biosynthesis to a different host organism to produce squalene. The ingredient is now used in its award-winning Biossance skincare range. Machine learning and big data techniques


are key enablers of the above approaches. Applying machine learning algorithms to DNA library databases facilitates the rapid discovery and enhancement of new enzymes for targeting DNA that occurs naturally in microorganisms. Alongside this, data analytics can


support cost-effective largescale production by identifying optimal parameters for microorganismal growth. This is particularly powerful if combined with technologies such as microreactors, which enable developers to test high numbers of different conditions in parallel. In the medical space, big data has already been used to identify more than 10,000 CRISPR systems, and this may allow the targeting of new sections of DNA that are inaccessible to Cas9


and other similar enzymes. Advancements


like this are likely to transfer to personal care in the coming years, which could facilitate convergence in areas where cosmetics and consumer healthcare currently run in parallel, such as the development of products for skin- related medical conditions including acne and eczema. Finally, the development of platform


recombinant expression systems of mammalian, plant, fungal (including yeast), microalgae, and bacterial origin allows for rapid scale-up of a range of biological ingredients. This reduces the complexity and capital cost of biotech production, aiding the creation of alternative biological ingredients.


PERSONAL CARE October 2023


Key drivers, benefits and barriers Obtaining key ingredients through SynBio techniques may offer better security and flexibility in production as well as improving consistency by reducing batch-to-batch variation. For example, Evolva emphasises ‘availability’ and ‘quality’ as core supply chain benefits for its fermentation-produced ingredient Nootkatone.5


Enhancing consistency


and constancy may have a beneficial impact on products’ safety assessments too. In theory, SynBio methods also offer


unlimited potential to produce ingredients with limited availability, such as those derived from endangered species. The Manool used to make woody, amber notes in the fragrance industry is one example. It is traditionally sourced from endangered Manoao pine trees in New Zealand, but Amyris’ fermentation-based process offers a sustainable, reliable, and consistent supply.6 With consumers demanding high-quality,


ethical, and sustainable personal care products, it would be easy for manufacturers to pin their hopes on this rise of SynBio techniques. However, major technical challenges still need to be addressed, especially in relation to versatility and scalability. It can also be difficult to fully integrate and streamline individual processes into automated SynBio workflows. Achieving commercial-scale production that


is cost-compatible with consumer products is widely seen as a major difficulty. Overall production costs remain high and can outweigh any marketing benefits. Hurdles include low yield of ingredients and ingredient expression variability as well as long production times and limited production capacity. The supply chain infrastructure is also immature, which exacerbates issues with costs as manufacturers pay market rates for materials. These issues are not insurmountable, but


they do require attention and investment in supporting technologies. A report published by Imperial College London’s bioengineering department, Frontier Manufacturing: Scaling up synthetic biology,7 success factors.


These include the need for new biologically based sensors that monitor production processes to enable real-time quality control. There is also a need for robust production cells that can tolerate high levels of compounds. In the meantime, the report suggests that intermediate production methods combining biological and chemical catalysts will be required.


A unison of academia and industry SynBio’s technical challenges are occupying attention at a global level, with extensive work underway in academic and commercial settings. A Kobe University team has developed the machinery to synthesise long chains of DNA for insertion into cells to bulk-edit genes. This precise tool is claimed to reduce the time taken for synthesis by half, as well as significantly cut the costs.8 Elsewhere, professors at Boston University’s


College of Engineering have worked on the development of next-generation software tools to streamline the design of synthetic biological systems, from concept to assembly.9 Academia-industry partnerships have also


been very fruitful. Imperial College London completed a multi-phase project in partnership with GlaxoSmithKline, Shell Global Solutions, Lonza Biologics and Dr Reddy’s Laboratories. It involved strategies for designing and optimising bio-based unit operations, the development of hybrid process systems, as well as platforms for artificial membrane compartmentalisation and cell extracts for manufacturing scale-up. Outputs include the production of novel


therapies and synthesis of commodity chemicals for renewable feedstocks.7


Clearly,


cross-sector learning and multi-disciplinary collaboration are to play a fundamental role in the development of SynBio solutions for largescale use in personal care applications. Notable commercial examples more


highlights several critical


closely related to personal care include Locus Performance Ingredients’ patented modular fermentation platform for bio-surfactant ingredients with a near-zero carbon footprint.


www.personalcaremagazine.com


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