Proteolysis-targeting chimera (PROTAC) is a heterobifunctional molecule. Typically, PROTAC consists of two terminals which are the ligand of the protein of interest (POI) and the specific ligand of E3 ubiquitin ligase, respectively, via a suitable linker. PROTAC degradation of the target protein is performed through the ubiquitin–proteasome system (UPS). The general process is that PROTAC binds to the target protein and E3 ligase to form a ternary complex and label the target protein with ubiquitination. The ubiquitinated protein is recognized and degraded by the proteasome in the cell. At present, PROTAC, as a new type of drug, has been developed to degrade a variety of cancer target proteins and other disease target proteins, and has shown good curative effects on a variety of diseases. For example, PROTACs targeting AR, BR, BTK, Tau, IRAK4, and other proteins have shown unprecedented clinical efficacy in cancers, neurodegenerative diseases, inflammations, and other fields. Recently, PROTAC has entered a phase of rapid development, opening a new field for biomedical research and development. This paper reviews the various fields of targeted protein degradation by PROTAC in recent years and summarizes and prospects the hot targets and indications of PROTAC.
The analysis of DNA methylation and MTase (methyltransferase) activity is important in epigenetic study. We have developed a novel strategy for sensitive analysis of MTase activity based on a hairpin shaped DNAzyme; 8–17 DNAzyme amplicon has been adopted and found to be very effective in such analysis.
We reported an efficient strategy based on a strand displacement amplification for serum miRNA detection. In such a system, a multiplexed, sensitive and quick detection of miRNAs could be achieved through a combination of fluorescence labeled probes, a common primer and a polymerase. This could be potentially used in the clinical field to achieve early disease diagnosis and prognosis.
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.
The present study demonstrated a highly sensitive strategy for measuring telomerase activity in cell extracts. Furthermore, we applied the new strategy for in situ detection of telomerase at the cellular level in cancer cells, together with a normal cell as the negative control.