Zynteglo (betibeglogene autotemcel) is the world's first gene therapy approved by the U.S. Food and Drug Administration on August 17, 2022 for adults and children with β-thalassemia who require regular blood transfusions. Zynteglo is a one-time gene therapy product administered as a single dose. Each dose of Zynteglo is a customized treatment created using the patient's own $\mathrm{CD}_{34}^{+}$ bone marrow hematopoietic stem cells which are genetically modified in vitro and then autologously transplanted. The modified stem cells will differentiate into red blood cells which are capable of producing functional hemoglobin, therefore achieving the purpose of β-thalassemia treatment. This paper provides a comprehensive introduction to the gene therapy from six aspects: lentiviral vector and mechanism of action, non-clinical research, clinical efficacy research, clinical safety research, indications and methods of use, and precautions.

Targeted protein degradation (TPD) strategies have been used by academia and industry as one of the promising new drug development technologies to address targeted proteins that are not effectively acted upon by conventional small molecule inhibitors. Protein hydrolysis-targeted chimeras (PROTAC) have become the most well-studied protein-targeted degradation technique in TPD, which comprises of a POI-binding ligand, an E3 ligand, and a linker connecting the two ligands. Once the POI ligand binds to the receptor protein, PROTAC recruits the E3 ligand to ubiquitinate the protein and finally degrades it through the ubiquitin-proteasome system. PROTAC technology offers great potential for therapeutic applications because it can target proteins that lack well-defined active degradation sites, which are often involved in the pathogenesis of cancer and other diseases. To enhance PROTAC's target delivery and tissue selectivity, the industry has begun to investigate new strategies, such as discovering new E3 ligases and developing corresponding ligands, along with continuing to investigate more emerging PROTAC modalities to further promote PROTAC. These strategies and relevant studies are discussed in this review.

This article reviewed the reports of adverse reactions of 17 weight-loss drugs approved by the FDA since 1887 during the clinical trials and after their marketing, including six that are still on the market and 11 that have been withdrawn due to valvular heart disease, suicidal tendencies, cancer risk, or other reasons. Weight-loss drugs can reduce weight and bring metabolic benefits in obese patients, but also cause various side effects, including psychonervous system adverse reactions, cancer risk, cardiotoxicity, liver damage, pancreatic toxicity, renal toxicity, digestive tract side effects, etc. Drugs with severe side effects will receive a black box warning from the FDA, and drugs with fatal side effects will be ordered to withdraw from the market. In addition to summarizing the side effects of weight-loss drugs, this article put forward some in-depth considerations on their safety, in order to provide reference for pharmaceutical companies to develop weight-loss drugs, clinicians and patients to use weight-loss drugs correctly and protect people's lives and health.

Roflumilast is a selective phosphodiesterase-4 inhibitor. Roflumilast 0.3% cream was approved by the U.S. FDA on July 29, 2022 (trade name Zoryve) for the treatment of plaque psoriasis in patients of 12 years or older, including intertriginous areas. Unlike other topical medicines, roflumilast has a higher safety profile, it is non-irritating to the skin, can be used continuously in long-term, and does not thin the skin. This article reviews its mechanism of action, pharmacokinetics, safety, clinical efficacy and precautions for use.

Nanocrystals possess the merits of high solubility, fast dissolution rate and high bioavailability with extremely small particle size, so they have been used in various formulations for oral, injectable, transdermal or mucosal delivery. Although injectable drug delivery is relatively reliable, the transport process of nanocrystals after injection is more complicated than that of solution. Based on literature research, this paper reviews the mechanisms of absorption, distribution, metabolism and excretion of injectable nanocrystals. Meanwhile, it also describes the factors affecting their processes in vivo, including the influence of physiological factors such as injection site, mononuclear phagocyte system, and formulation factors such as drug particle size and stabilizer. All of these provide a good foundation for further extensive application.

As a sensor of environment-cell interaction, aryl hydrocarbon receptor (AhR) plays an important role in maintaining barrier function, immune system and antioxidant process of the skin. AhR regulates the expression of many genes that are related to basic skin functions. It is expressed in all types of skin cells and involved in the progression of a variety of inflammatory skin diseases, including atopic dermatitis and psoriasis. Due to the complexity of the AhR protein structure, its crystal structure has not been successfully resolved until researchers obtained the crystal structure of indirubin binding to HSP90-XAP2-AhR complex recently. Clinical studies have shown that activation of the AhR pathway by ligands is of significance to the treatment of inflammatory skin diseases, as demonstrated by the clinical success of an AhR agonist, Benvitimod, for the treatment of psoriasis. This article presents a brief review on the role of AhR in inflammatory skin diseases and the current progress in drug development.

Model-informed drug development (MIDD) is a major shift of new mode of drug development based on the establishment of PK-PD model using blood concentration- (i.e., exposure, PK) and efficacy/safety (i.e., response, PD)-corresponding data, in order to analyze exposure-response relationship, replace dose-response relationship that is difficult to obtain, and establish the chain of evidence on drug safety and efficacy. The above model can integrate data from in vitro and in vivo, animals and human beings, adults and children, literature and trials, original and new dosage forms, domestic and foreign trials, and other sources to solve a wide range of key clinical problems. It is particularly important to transform the exploration paradigm of new drug development into a model verification mode. Therefore, MIDD is not only related to the change of technical means, but also the integration of multidisciplinary research, as well as a change of research and development strategy and scientific regulatory. It greatly improves the efficiency and success rate of new drug research and development. Based on the summary of MIDD success cases, this paper tries to clarify the basic principle, concept and method, implementation path, and takes anti-psoriasis monoantibody as an example to establish a complete MIDD working mode.