A potential paradigm in CRISPR/Cas systems delivery: at the crossroad of microalgal gene editing and algal-mediated nanoparticles

Abstract

Microalgae as the photosynthetic organisms offer enormous promise in a variety of industries, such as the generation of high-value byproducts, biofuels, pharmaceuticals, environmental remediation, and others. With the rapid advancement of gene editing technology, CRISPR/Cas system has evolved into an effective tool that revolutionised the genetic engineering of microalgae due to its robustness, high target specificity, and programmability. However, due to the lack of robust delivery system, the efficacy of gene editing is significantly impaired, limiting its application in microalgae. Nanomaterials have become a potential delivery platform for CRISPR/Cas systems due to their advantages of precise targeting, high stability, safety, and improved immune system. Notably, algal-mediated nanoparticles (AMNPs), especially the microalgae-derived nanoparticles, are appealing as a sustainable delivery platform because of their biocompatibility and low toxicity in a homologous relationship. In addition, living microalgae demonstrated effective and regulated distribution into specified areas as the biohybrid microrobots. This review extensively summarised the uses of CRISPR/Cas systems in microalgae and the recent developments of nanoparticle-based CRISPR/Cas delivery systems. A systematic description of the properties and uses of AMNPs, microalgae-derived nanoparticles, and microalgae microrobots has also been discussed. Finally, this review highlights the challenges and future research directions for the development of gene-edited microalgae. Graphical Abstract

Microalgae as a potential natural source for the green synthesis of nanoparticles

“…28,37–39 Also, microalgae can grow at colder temperatures and have a lower level of environmental toxicity (being efficient at fixing CO 2 ). Their metabolism produces less waste and greenhouse gas emissions compared to higher plants 36 and the are easy to manipulate genetically, allowing the optimization of the desired characteristics, 40 in addition to their potential for hyperaccumulating metals. 35 Microalgae are unicellular microorganisms and the basis of aquatic trophic chains, 41 and have long been used by humans as a vital source of nutrient-rich foods and health-promoting substances.…”

“…42 However, certain factors, such as an inadequate sterilization or culture conditions, can lead to contamination (bacterial and fungal), but modern technologies and good practices can mitigate this problem. 40…”

CRISPR Variants for Gene Editing in Plants: Biosafety Risks and Future Directions

“…However, ensuring biosafety remains a paramount concern in its application. Recent advances in nanotechnology have presented a promising avenue in plants toward enhancing the biosafety of CRISPR/Cas9 technology, creating a potential combination for sustainable genome engineering [57,58]. Nanotechnology can significantly improve the delivery methods of CRISPR/Cas9 components by manipulating matter at the atomic and molecular scale [57].…”

“…Recent advances in nanotechnology have presented a promising avenue in plants toward enhancing the biosafety of CRISPR/Cas9 technology, creating a potential combination for sustainable genome engineering [57,58]. Nanotechnology can significantly improve the delivery methods of CRISPR/Cas9 components by manipulating matter at the atomic and molecular scale [57]. Encapsulating the CRISPR/Cas9 system within nanoparticles can allow it to be delivered directly to the target cells, reducing off-target effects and enhancing precision [59,60].…”