CRISPR quality control on a chipAran, Kiana; Goldsmith, Brett R.
doi: 10.1038/s44222-024-00159-4pmid: 41393513
Combining the precision of CRISPR’s DNA searching ability with the speed and scalability of electronics, we have developed an ‘electronic DNA search engine’, called a CRISPR–Chip, which not only enables DNA detection without amplification, but also showcases the untapped potential of merging molecular biology with nanomaterial electronics. Here, we discuss highlights and challenges on the journey from the initial idea to the commercialization of the CRISPR–Chip.
The mechanisms of nanoparticle delivery to solid tumoursNguyen, Luan N. M.; Ngo, Wayne; Lin, Zachary P.; Sindhwani, Shrey; MacMillan, Presley; Mladjenovic, Stefan M.; Chan, Warren C. W.
doi: 10.1038/s44222-024-00154-9pmid: N/A
Nanoparticles for the detection and treatment of cancer have suffered from limited clinical translation. A key problem has been the lack of understanding of the mechanisms of nanoparticle delivery to solid tumours. The current delivery mechanism is called the enhanced permeability and retention effect, which states that nanoparticles passively enter the tumour through gaps between endothelial cells and are retained because of poor lymphatic drainage. However, nanoparticles designed according to the enhanced permeability and retention effect have limited delivery to solid tumours. An alternative mechanism proposes that nanoparticles enter the tumour through active endothelial transport processes, are retained in the tumour due to interactions with tumour components and exit the tumour through lymphatic vessels. This mechanism is called the active transport and retention principle. In this Review, we explore the contrasting views of these two mechanisms of nanoparticle delivery to solid tumours, explaining the underlying biological mechanisms and their effect on nanoparticle design for cancer applications. Defining the nanoparticle delivery mechanisms to solid tumours is crucial to the advancement and clinical translation of cancer nanomedicines and to determining how nanoparticles should be engineered for medical use.
Controlling the biodistribution and clearance of nanomedicinesCabral, Horacio; Li, Junjie; Miyata, Kanjiro; Kataoka, Kazunori
doi: 10.1038/s44222-023-00138-1pmid: N/A
Nanomedicines improve drug bioavailability, the dose–response relationship, targeting ability, efficacy and safety compared to conventional freely administered drugs. Nonetheless, despite their success as carriers for SARS-CoV-2 vaccines, clinical use of nanomedicines is still limited, probably caused by mismatches between animal models and humans. In this Review, we propose that improving blood circulation, biodistribution and tissue accessibility could help improve the clinical translation of nanomedicines. Specifically, we emphasize control of the pharmacokinetics relevant to the administration route, therapeutic targets in tissues and cells, and the drug payloads. Furthermore, we analyse the clearance and distribution of nanomedicines in preclinical and clinical studies, highlighting the biological barriers determining their in vivo performance. Finally, we present engineering strategies, such as size tuning, active targeting for transcytosis, external stimuli and biological shifts, to overcome these barriers.
Engineered autonomous dynamic regulation of metabolic fluxReam, Michael; Prather, Kristala L. J.
doi: 10.1038/s44222-023-00140-7pmid: N/A
Metabolic engineering is a powerful tool to reprogramme cells to produce value-added chemicals. Such engineering strategies require the fine-tuning of a cell’s metabolism to balance competition for resources and prevent negative impacts on growth. Dynamic regulation enables the shifting of resources or metabolic flux toward different pathways based on a received input to increase titres of value-added chemicals in microbial production strains. In this Review, we discuss autonomous dynamic regulation, that is, responses triggered directly by a stimulus without the need for human intervention, and its application to metabolic engineering. We highlight strategies to control the transcription of genes using metabolite-specific regulation, including by transcription factors and through biosensing, and non-specific regulation, in particular, environmental regulation, growth-phase responses and quorum sensing, examining the application of these regulation strategies to the bioproduction of different chemicals.