如果我们可以通过单一方法来治疗甚至治愈疾病，该有多好？基因治疗的愿景，是可以纠正疾病的潜在遗传原因。尽管基因疗法具有令人兴奋的潜力，但由于安全性和有效性方面的问题，以及早期临床试验的失败强调需要进一步深入了解基因疗法的基础科学。欢迎了解 NanoTemper 是如何帮助研究人员开发更安全，更有效的基因疗法。
In order to design a good gene therapy vector, researchers must consider not only capsid formation and structure, but also how well it delivers the genetic payload to the cell. Gene therapy optimization requires understanding how much genetic material is loaded into the vector, as well as the mechanism of payload release. Avoiding the loss of DNA or RNA during storage and transport is also a critical concern for those working in scale-up and manufacturing of gene therapy products.
Monitor vector stability and prevent DNA loss in AAVs
Manufacturing a successful gene therapy vector relies on the stability of its capsid. This means not only ensuring the capsids are serotyped properly, but also that none of the genetic material is lost over the course of the manufacturing process. This group used nanoDSF to probe vector stability and relate it to the amount of DNA lost in different storage conditions.
基因编辑技术可以通过有针对性地对体内基因组进行编辑（包括基因添加，删除和校正）来提供基因治疗。尤其是，CRISPR-Cas9 体系为治疗遗传性疾病提供了令人兴奋的新的可能性。现在，研究人员正在努力通过使用 Cas9 的变体来消除脱靶编辑或寻找可替代的递送系统来使基因编辑工具变得更安全可靠。
使用其他 Cas9 变体提高基因编辑特异性
Gene editing with CRISPR-Cas9 has shown great promise in the treatment of diseases such as sickle cell anemia. However, off-target gene editing has been reported for some Cas9 proteins, like SpCas9. This study used MST to show that a different variant of Cas9, FnCas9, has a higher specificity for its intended target and low off-target binding. FnCas9 was then used to successfully correct sickle cell mutations in the patient-derived pluripotent stem cells.
The use of viral vectors still raises concerns about safety due to off-target delivery of nucleic acids. To improve target specificity, the authors designed a chromatin-based nucleic acid delivery system that incorporates antibodies specific to cell surface elements. The key to the success of this system is the efficient capture of the antibody to the chromatin, and MST was used to quantify the interaction between different antibodies and the chromatin. This allowed them to find the best antibody for constructing a highly efficient and specific chromatin-based delivery system for CRISPR-Cas9 gene editing.