Erfolg bei den ersten menschlichen Experimenten: Gen-geditierte Inselzellen wurden "unsichtbar" implantiert und können normal Insulin sezernieren.

A new breakthrough in diabetes treatment!

The latest research shows that scientists have for the first time transplanted CRISPR-edited islet cells into a patient with type 1 diabetes.

These cells not only continuously secrete insulin for several months but also evade immune detection, eliminating the need for the recipient to take immunosuppressants.

This research has been published in the New England Journal of Medicine and was reported as news on the official website of Nature.

So, how exactly was this breakthrough achieved?

CRISPR gene editing brings hope for treating diabetes

Type 1 diabetes is an autoimmune disease in which the patient's immune system mistakenly attacks the insulin-secreting cells in the pancreas.

Once insulin production stops, blood sugar in the body gets out of control.

If insulin is not supplemented through injection or other means, this disease can damage nerves and organs, especially the heart, kidneys, and eyes.

In response to this problem, Sana Biotechnology in Seattle, Washington, has proposed a new study, bringing hope for a cure to about 9.5 million patients with type 1 diabetes worldwide.

First, at Uppsala University Hospital, researchers extracted islet cells from a 60-year-old cadaver donor without diabetes.

Subsequently, these cells were transported to Oslo University Hospital and modified using the CRISPR-Cas12b gene editing technology.

The main approach was to knock out two key genes - B2M (class I HLA) and CIITA (class II HLA). These two genes usually mark foreign invaders to T cells (the frontline defenders of the immune system).

Subsequently, to deal with the attacks of immune sentinels such as natural killer cells, the researchers took further measures.

They introduced the gene encoding the CD47 protein into these cells through a viral vector. This protein can send a "don't eat me" signal to confuse the immune system.

In the edited islet cells, 85.8% of the cells no longer had class I HLA molecules, all cells had no class II HLA molecules, and 46.4% of the cells highly expressed the CD47 protein on their surface.

Finally, the gene-edited islet cell preparation UP421 consists of three types of cells:

Fully edited HIP islet cells lacking HLA and highly expressing CD47;

Cells with partial double knockout of class I and class II HLA and maintaining endogenous levels of CD47;

Islet cells retaining HLA expression (wild type) with varying levels of CD47.

Then, these edited islet cells were transported back to Uppsala University Hospital for implantation.

A 42-year-old patient who had suffered from type 1 diabetes for 37 years was given general anesthesia, and a surgical incision about 3.8 cm long was made above the left brachioradialis muscle.

The researchers divided a total of 79.6 million engineered HIP islet cells into 17 syringes and implanted them into the muscle tissue through 17 injections.

During each injection, the doctor slowly withdrew the syringe, allowing the islet cells to be linearly arranged in the muscle in a "string of pearls" pattern.

After the operation, the patient was observed in the hospital overnight to monitor for immediate complications and was discharged smoothly the next day.

It is worth noting that no glucocorticoids, anti-inflammatory drugs, or immunosuppressive drugs were used during the entire treatment process.

The study shows that 12 weeks after transplantation, these gene-edited islet cells not only showed no signs of rejection but also continuously secreted insulin, effectively regulating the patient's blood sugar level.

As a direct marker of endogenous insulin secretion, the C-peptide level could not be detected at the baseline but was significantly elevated at the 4th, 8th, and 12th weeks after the intervention.

Moreover, according to a subsequent report released by Sana Biotechnology, even 6 months after transplantation, these cells can still effectively evade recognition and attack by the immune system.

However, it should be noted that this study only involved one participant, who received a low-dose cell treatment, and the treatment time was short, which is not enough for the patient to no longer need to inject insulin to control blood sugar.

Based on this, Sana plans to conduct more clinical trials starting next year for a more comprehensive study.

Reference links:

[1]https://www.wired.com/story/no-more-injections-crispr-offers-new-hope-for-treating-diabetes

[2]https://www.nature.com/articles/d41586-025-02802-5

[3]https://www.nejm.org/doi/full/10.1056/NEJMoa2503822

This article is from the WeChat official account “QbitAI”. Author: Shiling. Republished by 36Kr with permission.