Nucleic acid aptamers are single-stranded oligonucleotides with the ability to specifically bind to target molecules. Currently, nucleic acid aptamers are screened from large random nucleic acid libraries using SELEX technology. It can identify different types of target molecules such as proteins, viruses, bacteria, cells, etc. Nucleic acid aptamers not only have the specificity of antibodies, but also have many advantages over antibodies, such as a wider range of target molecules, better thermal stability, smaller molecular weight, chemical synthesis, small batch differences and easy modification. Therefore, nucleic acid aptamers have broad application prospects in biomedicine, diagnostic testing, drug development and other fields, but they also face challenges such as patent restrictions…

At present, genetic diseases are a large category of diseases that affect human health. So far, we can only treat a small part of them, and most of the treatment methods are “treating the symptoms but not the root cause”. Therefore, gene therapy that can “cure the root cause” is highly anticipated. Gene therapy is a treatment method that uses modern molecular biology methods to repair disease-causing genes to achieve relief and cure of diseases. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) system won the Nobel Prize for related discoveries just a few years later, showing its vigorous vitality in gene editing. In gene therapy, safe…

As an intermediate carrier, mRNA can transfer the genetic code in DNA to ribosomes for protein expression. It has great potential in vaccines, protein replacement therapy, and gene editing. Compared with traditional small molecule and protein drugs, mRNA-based therapies show some specific advantages in terms of safety, efficacy and preparation. However, despite these potential advantages of mRNA, how to deliver it safely, efficiently, and stably within cells remains an important obstacle. In recent years, nanobiotechnology has made significant progress, providing important tools for the development of mRNA nanocarriers. Nanocarrier systems can be directly used to load, protect, and release mRNA in biological microenvironments, and can be used to stimulate mRNA…

Many clinical trials of mRNA-based drugs or vaccines have failed to successfully pass Phase I or Phase II. The reasons behind this are various, including low efficacy of candidate drugs and lower-than-expected clinical risk/treatment benefit profiles. Preclinical safety assessments aim to identify well-tolerated and efficacious LNP-mRNA formulations, and when toxicity is observed, in vivo, in vitro and ex vivo experiments aim to understand the underlying mechanisms and, ideally, improve the formulations design under development. The main safety issues of LNP-mRNA preparations in preclinical development can be divided into immunopathogenicity and liver and spleen toxicity (only studies on modified and/or dsRNA-purified mRNA are considered). Understand the different formulations of LNP-mRNA preparations…

Gene therapy is the transfection of genes (plasmid DNA, siRNA and miRNA, etc.) into specific cells to promote or inhibit the expression of the target protein to achieve the purpose of treating human diseases. Because RNA and DNA gene fragments are negatively charged and are easily degraded by nucleases, it is difficult to pass through negatively charged cell membranes. Therefore, selecting appropriate gene carriers to protect and transport gene fragments into cells is an urgent problem to be solved. Viral vectors and non-viral vectors are the two most commonly used gene transfer vectors. Although viral vectors have high transfection efficiency, their shortcomings such as immunogenicity, tumorigenicity, and difficulty in mass…

Gene therapy is the introduction of exogenous normal genes or genes with therapeutic effects into target tissues or target cells through vectors or other means, and appropriate expression to treat diseases. The key of gene therapy is to obtain efficient and safe gene delivery vectors. Vectors for gene delivery are generally classified into viral vectors and non-disease vectors. Viral vectors are the most widely used gene vectors, including retroviruses, adenoviruses, adeno-associated viruses and lentiviruses. The biggest advantage of viral vectors is the high transfection rate, but they also have many disadvantages, such as the difficulty of virus preparation, the limited size of loaded foreign DNA, cytotoxicity, immunogenicity, carcinogenicity, etc., and…