Hereditary deafness is a common neurosensory disorder, and 148 nonsyndromic deafness genes have been identified to date. Gene therapy has been used to treat a variety of genetic diseases, but no gene therapy drug for hereditary deafness has been approved for clinical use. At present, several clinical trials of gene therapy for hereditary deafness are underway. However, few normative documents have been issued to guide the standardization of gene therapy for hearing loss, and this document is the first global gene therapy guideline for hereditary hearing loss. The guidelines were jointly developed and drafted by experienced audiologists, virologists and biologists who are vigorously involved in inner ear gene therapy research in the Hearing, Speech and Communication Subsociety of Biophysical Society of China, Audiology Development Foundation Of China and Audiology Subsociety of Jiangsu Medical Association. These guidelines cover preclinical research and clinical practice of gene therapy for hereditary deafness, including indications, key points of pre-clinical research, patient selection criteria, pre-clinical preparation, drug efficacy, drug safety evaluation criteria, ethical review, etc. We hope that the guidelines will promote the standardization of clinical practice related to gene therapy for hereditary deafness in China and around the world.

Bacteria have been explored for their potential in fighting against cancer for decades. Due to their outstanding tumor-targeting capacity and high biocompatibility, live bacteria can serve as microrobots delivering and producing anti-tumor agents. In addition, live bacteria have intrinsic immuneactivating functions that aid in the generation of anti-tumor immunity both systemically and locally in the tumor microenvironment. While bacteria-based cancer therapy is still facing great challenges, progress in this platform combined with nanobiotechnologies has shown promise in terms of safety and effectiveness. Here, basic development strategies of bacteria-based delivery systems armed with nanotechnologies, virulence attenuation, and genetic manipulation are summarized and the design of a spatiotemporal selectivity is particularly emphasized. In conclusion, the engineered bacteria platform has a high potentiality in the development of novel cancer therapeutics and holds prospects for future investigation and clinical use.

Biological particle separation has wide applications in medical diagnosis, bioengineering, and various other domains. Traditional methods, such as filtration, density gradient centrifugation, and size exclusion chromatography, face many challenges, including low separation resolution, low purity, and the inability to be seamlessly integrated into continuous processes. The development of microfluidics has paved the way for efficient and precise biological particle separation. Microfluidic chip-based methods can generally be performed continuously and automatically, and microfluidic chips can integrate multilevel operations, including mixing, separation, detection, and so forth, thereby achieving continuous processing of particles at various levels. This review comprehensively investigates biological particle separation techniques based on microfluidic chips. According to the different sources of force effect on the particles during the separation process, they can be divided into active separation, passive separation, and affinity separation. We introduce the principles and device design of these methods respectively, and compare their advantages and disadvantages. For the introduction of each method, we used the most classic and latest research cases as much as possible. Additionally, we discussed the differences between experimental standard particles and biological particles. Finally, we summarized the current limitations and challenges of existing microfluidic separation techniques, while exploring future trends and prospects.

Some biomolecules involved in pathological calcification have been identified. However, the exact mechanism in which this intricate process occurs remains unknown. Extracellular DNA (exDNA) has recently been recognized as a partaker in this ectopic phenomenon. Extracellular DNA acts as an intercellular messenger that transmits information and orchestrates complex inflammatory responses. Changes in the morphology or function of exDNA may trigger calcification under pathological conditions. In the present review, recent advances on how DNA is released into the extracellular milieu to become exDNA will be highlighted in conjunction with how exDNA directly and indirectly contributes to the progression of pathological calcification. Emphasis is placed on the “gluing” effect of neutrophil extracellular traps that act as a bridge between inflammation and pathological calcification. Manipulation of exDNA may open new vistas for the development of enterprising strategies that prevent or treat pathological calcification.

Body temperature variations, including the generation, transfer, and dissipation of heat, play an important role throughout life and participate in all biological events. Cellular temperature information is an indispensable link in the comprehensive understanding of life science processes, but traditional testing strategies cannot provide sufficient information due to their low precision and inefficient cellular-entrance. In recent years, with the help of luminescent nanomaterials, a variety of new thermometers have been developed to achieve real-time temperature measurement at the micro/nano scale. In this review, we summarized the latest advances in several nanoparticles for cellular temperature detection and their related applications in revealing cell metabolism and disease diagnosis. Furthermore, this review proposed a few challenges for the nano-thermometry, expecting to spark novel thought to push forward its preclinical and translational uses.

As emerging alternatives to natural enzymes, nanoscale materials featuring enzyme-like catalytic behaviors (nanozymes) exhibit some attractive merits including robust activity, low cost, and easy-to-regulate performance. These merits have enabled them to be intensively used in the biomedical field in recent years. To remedy the lack of catalytic selectivity in most nanozymes, deoxyribonucleic acid (DNA) chains with specific recognition functions are utilized to integrate with nanozymes to produce various nanozyme-DNA combinations via adsorption/desorption. In the formed combinations, the DNA component provides the molecular/ionic recognition role, and the nanozyme part offers response with catalytically amplified signals, enabling them to detect analytes and biomarkers selectively and sensitively. To highlight this interesting topic, here we made a critical review of the interactions between nanozymes and DNA and their applications in biosensing and disease diagnosis. First, strategies for the conjugation of DNA chains onto nanozyme surface were introduced briefly. Then, the interactions between DNA and nanozymes were summarized in detail, where flexible modulations of nanozyme activity by DNA adsorption/desorption as well as various factors were analyzed, and potential impacts caused by nanozymes on the recognition characteristics of DNA chains were pointed out. After that, typical applications of DNA-mediated nanozyme modulation in toxic ion sensing, health risk factor monitoring, and biomedical diagnosis were introduced. In the end, prospects of the combination of nanozymes and DNA chains were presented, and future challenges of the emerging field were also discussed, to attract more interest and effort to advance this promising area.

T cells engineered to express chimeric antigen receptors (CARs) with specificity toward tumor cells have led to promising outcomes in patients with hematological malignancies. Nevertheless, the application of CAR-T cell therapy in solid tumors encounters several obstacles. These include tumor heterogeneity and immune escape, T cell exhaustion and restricted infiltration into the tumors that affect the therapeutic efficacy of CAR-T cells, as well as “on-target, off-tumor” toxicities that can lead to severe and even fatal adverse events. In recent years, clinical trials and new approaches of CAR-T cell therapy for solid tumors have made certain progress. Here, we update the outcomes of related clinical trials and summarize engineered strategies aiming to improve the efficacy and therapeutic safety of CAR-T cells based on experimental and clinical studies.

The field of DNA nanotechnology has evolved beyond the realm of controllable movements and randomly shaped nanostructures, now encompassing a diverse array of nanomachines, each with unique nanostructures and biofunctional attributes. These DNA nanostructures boast exceptional characteristics such as programmability, integrability, biocompatibility, and universality. Among this variety, DNA walking nanomachines have emerged as one of the most prominent nanomotors, distinguished by their ingenious design and comprehensive functionality. In recent times, these DNA walkers have witnessed remarkable advancements in areas ranging from nanostructural designs to biological applications, including the creation of sophisticated biosensors capable of efficiently detecting tumor-related biomarkers and bioactive substances. This review delves into the operational mechanisms of DNA walking nanomachines, which are driven by processes such as protease and DNAzyme action as well as strand displacement and photoactivated reactions. It further provides a comprehensive overview of DNA walking nanomachines with different dimensional (1D, 2D, and 3D) walking tracks. A subsequent section introduces the biosensing applications of DNA walking nanomachines including electrochemical, optical, and other biosensors. The review concludes with a forward-looking perspective on the novel advancements and challenges in developing DNA walking nanomachine-based biosensors.

Infectious diseases pose significant threats to public health and the global economy, necessitating rapid and accurate detection of the causative microorganisms to prevent their transmission. Nanomaterials, with their unique size-dependent physical and chemical attributes, present innovative solutions for the detection of infectious diseases, thereby playing a crucial role in the development of advanced detection technologies. This review describes the application of inorganic nanomaterials in the detection of infectious diseases, focusing on the potential uses of nanomaterials, including carbon nanoallotropes, quantum dots, gold and silver nanoparticles, magnetic nanoparticles and upconversion nanoparticles.

Tuberculosis (TB) is a fatal infectious disease that continues to pose a serious public health threat. The emergence of drug-resistant TB has further worsened the burden of the disease. The interaction between the host and the pathogen involves multiple modes of cell death, which play a role in determining immune outcomes. Several studies have established a strong correlation between cell death and TB progression. This review explores the molecular mechanisms of various cell death modes in Mycobacterium tuberculosis (Mtb) infection and how Mtb’s virulence effectors regulate these pathways, including apoptosis, autophagy, pyroptosis, ferroptosis, and necrosis. Furthermore, therapeutic strategies targeting cell death pathways have shown promising results in TB treatment. Importantly, this review highlights the significant potential of mitochondria in mediating communication between different cell death modes and influencing the final outcomes. Overall, this work provides a comprehensive summary of the role of cell death in host immune responses and immune evasion by Mtb. It also offers valuable insights into the pathogenesis of TB and immune evasion strategies employed by Mtb and contributes to the development of more effective anti-TB therapies.

Monitoring tumor biomarkers in a non-invasive manner for tumor diagnosis has attracted increasing attention. Liquid biopsy mainly includes three types of biomarkers: circulating tumor cells, extracellular vesicles, and circulating nucleic acids. These biomarkers released by tumor cells can travel to other parts of the circulation system. The analysis of circulating tumor markers in the circulation enables early tumor diagnosis, progression evolution, and treatment monitoring, which are important for individualized clinical decisions. In this study, we summarize different DNA nanotechnology strategies that can be used to capture, amplify, and measure circulating biomarkers and discuss the current challenges and outlook.

Over the two decades, RNA drugs have gradually made their way from bench to bed. Initially, RNA was not an ideal drug since RNA molecules degrade easily and have a relatively short half-life in the circulation system. Nevertheless, the chemical modification extended the half-life of RNA in recent years, which makes RNA drugs a new star in drug discovery industry. RNA molecules hold many properties that facilitate their application as therapeutic drugs. RNAs could fold to form complex conformations to bind to proteins, small molecules, or other nucleic acids, and some even form catalytic centers. Protein-encoding RNAs are the carriers of genetic information from DNA to ribosomes, and various types of non-coding RNAs cooperate in the transcription and translation of genetic information through various mechanisms. To date, three mainstream RNA therapies have drawn widespread attention: (1) messenger RNA that encodes therapeutic proteins or vaccine antigens; (2) small interfering RNA, microRNA (miRNA), antisense oligonucleotides that inhibit the activity of pathogenic RNAs; and (3) aptamers that regulate protein activity. Here, we summarized the current research and perspectives of RNA therapies, which may provide innovative highlights for cancer therapy.

Recent research underscores the significance of the nervous system in tumor progression. Nonetheless, understanding the intricate roles of nerves in gastric tumorigenesis remains limited. Our study aims to elucidate nerve alterations, associated key genes, and signaling pathways during gastric tumorigenesis. We enroll 257 patients with gastric precancerous lesions (GPLs) from four national cohorts. Utilizing immunohistochemistry and digital analysis, we quantified the densities of sympathetic and parasympathetic nerves, as well as Schwann cells in patient slides. We collected three mRNA expression profiles of GPL samples from the gene expression omnibus database and assessed them for nerve expression signatures, differentially expressed genes, enriched pathways, and the immune microenvironment. Parasympathetic nerve and Schwann cell densities display a progressive increase, while sympathetic nerve exhibits an inverse trend along the precancerous spectrums. Notably, CD8+ T cells, natural killer cells, and antigen-presenting cells (APC) co-inhibition decrease, while epithelial-mesenchymal transition increases significantly from early to late premalignancy. Several key nerve-regulating genes (NTRK3, MYBL2, NRP1, BCL2, CCND1, VEGFA, PLXNA2, ADRB2), and pathways (mitogenactivated protein kinase [MAPK]/ERK, PI3K/AKT, Wnt) emerge as potential contributors to precancerous progression. Our study reveals a dynamic relationship between sympathetic and parasympathetic nerves, characterized by a gradual increase in parasympathetic nerve and Schwann cell density, contrasting with an inverse trend in sympathetic nerve across precancerous spectrums. Targeting the interaction between tumor cells and nerves, including sympathetic and parasympathetic nerves, has emerged as a promising strategy for the prevention and treatment of gastric cancer.

With the increasing prevalence of infectious diseases caused by drug-resistant bacteria, there is an urgent need to develop innovative therapies alternative to antibiotics. Among these alternatives, the aggregation-induced emission (AIE) photosensitizers (PSs) stand out with their integrated imaging and therapeutic functionalities, allowing for early monitoring and image-guided ablation of bacteria. AIE fluorescent probes with unique optical properties excel in selective bacterial imaging. Furthermore, AIE-enabled reactive oxygen species (ROS)-mediated antibacterial photodynamic therapy can operate on multiple targets to oxidize bacteria. Also, as they are able to specifically target bacteria, AIE PSs can ameliorate the limitations of the small-scale action of ROS. This review methodically discusses the different strategies that can be employed using AIE PSs for targeting bacteria, including sheltered bacteria. The challenges and future opportunities of using AIE PSs in this emerging field are also briefly discussed.

Non-viral vector chimeric antigen receptor (CAR)-T cells have garnered increasing attention due to their ability to efficiently eradicate cancer cells while mitigating undesirable side effects. However, the current methods for engineering chimeric antigen receptor T (CAR-T) cells employ viral vectors that result in permanent CAR expression and potentially severe negative impacts. As a solution to these challenges, triggering transitory expression of CARs in T cells via messenger RNA (mRNA) has emerged as a promising strategy. Currently, electroporation is a common method used to introduce the mRNA encoding the CAR into the T cells. Moreover, there has been increasing attention on the exploration of innovative mRNA delivery systems, including lipid, polymer-based nanoparticle, exosomes and peptide transduction domains. Additionally, we also explored the functions of different types of mRNA in mRNA-based CAR-T cell therapy. The auxiliary mRNA, exemplified by systems such as megaTAL and nuclease transposon systems, demonstrates its capacity to extend CAR-T cell viability and survival. This perspective offers the current state of mRNA-based CAR-T cell therapy and provides valuable insights into future research avenues.