调节治疗性蛋白质释放以应对昼夜生物标志物的反应
Nik Franko1, Shichao Li2, Silvia Galvan1
1Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Nature communications
|November 6, 2025
概括
科学家们设计了一种新的黑激素诱导基因开关. 这个系统精确地控制治疗性基因表达,为每天一次针对糖尿病等疾病的细胞疗法提供了潜力.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 时间生物学 时间生物学
背景情况:
- 人类的昼夜时钟通过振荡的内分泌信号来调节生理过程.
- 识别这些节奏的分子传感器对于治疗应用至关重要.
研究的目的:
- 设计一种可诱导黑素的基因开关,以精确控制转基因表达的时间.
- 探索黑激素受体1A (MTNR1A) 作为基于昼夜节律的疗法的分子传感器的潜力.
主要方法:
- 通过异位表达的MTNR1A和Gαs信号级联设计了一个基因开关.
- 利用腺环酶,cAMP,蛋白激酶A和CREB来驱动转基因表达.
- 在植入于小鼠的酸盐封装细胞中展示了概念验证.
主要成果:
- 工程系统对生理夜间的黑激素水平做出了反应,而不是白天的水平.
- 仅在夜间实现调节GLP-1表达,以应对昼夜输入或激动剂.
- 在生理学黑激素度范围内展示了时间控制.
结论:
- 开发了一种具有精确时间控制的新黑色素诱导基因开关.
- 这个系统对个性化的细胞和基因疗法具有前景,需要每天服用一次的剂量方案.
- 作为一种实验性细胞治疗肥胖依赖型2型糖尿病的潜在应用.
相关概念视频
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
338
Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
338
Circadian Rhythms and Gene Regulation
4.5K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.5K
Therapeutic Drug Monitoring: Overview and Classification
282
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood at designated intervals to ensure the drug concentration stays within a therapeutic range. This monitoring is crucial for optimizing individual dosage regimens, enhancing therapeutic efficacy, and minimizing drug-related toxicity. TDM is vital for drugs with narrow therapeutic windows, significant variability in pharmacokinetics, and a clear correlation between plasma levels and...
282
Feedback Loops
63.6K
In most cases, excessive hormone production is prevented by negative feedback—a loop that starts with a stimulus inducing the release of a particular substance, like a hormone, to maintain a certain level before triggering a signal that results in a decrease in further release of the hormone.
63.6K
Therapeutic Drug Monitoring: Affecting Factors
189
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
189
Regulation of Hormone Secretion
6.1K
Regulation of hormone secretion is a finely tuned orchestration driven by various types of stimuli, encompassing neural, humoral, and hormonal signals. Environmental cues instigate neural stimuli, where action potentials traverse nerve fibers to reach their designated targets. An illustrative scenario is the body's response to stress, wherein the sympathetic nervous system releases epinephrine from the adrenal glands, inducing the well-known 'fight or flight' reaction.
Humoral...
Humoral...
6.1K


