Advances in lipid nanoparticle mRNA therapeutics beyond COVID-19 vaccines.

The remarkable success of two lipid nanoparticle-mRNA vaccines against coronavirus disease (COVID-19) has placed the therapeutic and prophylactic potential of messenger RNA (mRNA) in the spotlight. It has also drawn attention to the indispensable role of lipid nanoparticles in enabling the effects of this nucleic acid. To date, lipid nanoparticles are the most clinically advanced non-viral platforms for mRNA delivery. This is thanks to their favorable safety profile and efficiency in protecting the nucleic acid from degradation and allowing its cellular uptake and cytoplasmic release upon endosomal escape. Moreover, the development of lipid nanoparticle-mRNA therapeutics was already a very active area of research even before the COVID-19 pandemic, which has likely only begun to bear its fruits. In this Review, we first discuss key aspects of the development of lipid nanoparticles as mRNA carriers. We then highlight promising preclinical and clinical studies involving lipid nanoparticle-mRNA formulations against infectious diseases and cancer, and to enable protein replacement or supplementation and genome editing. Finally, we elaborate on the challenges in advancing lipid nanoparticle-mRNA technology to widespread therapeutic use.

Sperm-like nanocarriers for ultrafast delivery of antisense DNA.

Although various nanomaterials have been designed as intracellular delivery tools, the following aspects have become obstacles to limit their development, like a complex and time-consuming synthesis process, as well as relatively limited application areas (i.e. biosensing or cell imaging). Here, we developed a novel nano-delivery system called "nano-sperm" with low cytotoxicity and high biocompatibility. In this system, we used DNA oligonucleotides as a backbone to synthesize a nanostructure with silver nanoclusters in the head and functional fragments in the tail, which is shaped like a sperm, to achieve dual functions of ultrafast delivery and imaging/therapy. As a model, we analyzed the possibility of the "nano-sperm" carrying DNA with different structures for imaging or survivin-asDNA for tumor therapy. Therefore, this work reports a novel bifunctional high-speed delivery vehicle, which successfully fills the gap in the field of tumor therapy using DNA-templated nanoclusters as a delivery vehicle.

In situ Analysis of Cancer Cells Based on DNA Signal Amplification and DNA Nanodevices.

Cancer is a global disease which has been disturbing researchers in medicine and seriously threatens patients' health and lifetime around the world in the past several decades. Due to the characteristics of cancer cells, such as uncontrollable cell proliferation, cell invasion and metastasis to surrounding tissues, lower grade of differentiation, higher telomerase activity and others, it has been one of the most usual lethal factors, next to heart disease in incidence. Cancer mortality can be decreased by early diagnosis, and the people who with treatment at an early stage have an obvious improved survival rate. Consequently, early detection is significant for better understanding the pathogenesis of cancer and improving the prognosis of patients. In situ detection technique is a vital tool for imaging and cellular pathology research, which can provide effective information about tumor markers in the early cancer detection. In view of low expression of most tumor markers in the early stage of cancers, detection techniques based on DNA signal amplification and DNA nanodevices can provide a strong support for the diagnosis and detection of cancers. In this review, we summarize the research progress of different analytical techniques for detecting various tumor markers that have been reported in recent years. We compare different DNA amplification and nanodevices, then provide guidance and suggestions for better understanding in situ analysis of cancer cells.

Application of DNA nanodevices for biosensing.

Deoxyribonucleic acid (DNA), the carrier of genetic information in living life, is an essential biomacromolecule in almost all living systems. DNA has advantages including, programmability, predictability, high rigidity, and stability. Through self-assembly or combination with other nanomaterials (such as gold nanoparticles, graphene oxides, quantum dots, and polymers), DNA can be applied to construct specific, stable, biocompatible, and functional nanodevices. DNA nanodevices have made greater contributions in a plethora of fields. In this review, we discuss the recent progress of DNA nanodevices in molecular detection and analysis. Meanwhile, we prospect the development of various DNA devices in biological analysis, clinical diagnosis and biomedical research.