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▎The editing of WuXi AppTec's content team's biological products are increasingly used to treat inflammatory diseases, such as rheumatoid arthritis (RA)
.
However, about 40% of RA patients do not respond to treatment, and continuous high-dose administration will suppress the immune system, which may cause serious adverse reactions, such as increasing the risk of infection
.
Recently, scientists have used CRISPR-Cas9 genome editing technology to transform induced pluripotent stem cells (iPSCs)
.
These cells can be implanted subcutaneously.
In the RA mouse model, once inflammation occurs, the implanted "smart" cells will automatically sense the changes in the level of endogenous inflammatory cytokines and respond to deliver a corresponding therapeutic level.
Anti-inflammatory biological products can significantly reduce inflammation and completely prevent bone erosion
.
▲The paper was published in the peer-reviewed journal Science Advances (picture source: screenshot of the paper page) Biological products usually target several inflammatory cytokines and pathways, including interleukin-1 and -6 (IL-1 and IL-6) ), tumor necrosis factor -α (TNF-α) and the like
.
However, over time, the severity of RA disease may fluctuate.
When using these drugs for injection or infusion therapy, regardless of the patient's cytokine level or RA symptoms, they tend to be administered continuously at higher concentrations.
, Leading to adverse reactions
.
Therefore, the development of specific treatment strategies that can sense and respond to the levels of endogenous inflammatory factors is expected to reduce unnecessary side effects when effectively treating patients
.
A research team from Washington University School of Medicine in St.
Louis, USA, used CRISPR-Cas9 genome editing technology to transform induced pluripotent stem cells (iPSCs), and constructed cartilage stem cells (Stem cells) called “SMART”.
Cells Modified for Autonomous Regenerative Therapy), a synthetic gene circuit that is regulated by IL-1 to produce IL-1 receptor antagonist (IL-1Ra) is implanted in the cells
.
IL-1 promotes inflammation of arthritis by activating inflammatory cells in joints
.
When inflammation occurs, the gene circuit in the cell will sense the level of endogenous IL-1 cytokine and be activated to secrete IL-1Ra corresponding to the therapeutic level
.
▲The principle of the treatment plan (picture source: reference [1]) Professor Farshid Guilak, the corresponding author of the paper, explained, “We used CRISPR technology to re-edit the genes in the stem cells, and then by seeding the cells on the braided scaffold, Created a small cartilage implant and placed it under the skin of the mouse
.
This method allows these cells to exist in the body for a long time, and once an inflammatory response occurs, the corresponding proportional drug will be secreted
.
" Interestingly, although IL-1Ra has been proven to improve symptoms in animal models, it is not often used to treat rheumatoid arthritis because of its short half-life and average efficacy
.
However, this innovative self-regulating therapy of stem cells + implanted biological scaffolds overcomes the half-life and curative effects of drugs
.
Researchers found that IL-1Ra drugs significantly reduced joint inflammation and pain in mice
.
Moreover, when using radioactive imaging technology to observe bones, the drug inhibits bone damage commonly seen in rheumatoid arthritis and completely eliminates bone erosion
.
Bone erosion is bone destruction caused by disease deterioration.
Current treatments cannot effectively deal with it.
Therefore, there are important unmet clinical needs
.
Even better, researchers can also use CRISPR-Cas9 gene editing technology to create different types of drugs
.
In other words, if one therapeutic drug works better than another in a particular patient, it may be possible to develop individualized therapies by reprogramming chondrocytes
.
This treatment plan also has great potential to treat other inflammatory arthritis diseases, including juvenile arthritis
.
Researchers are continuing to experiment with CRISPR-Cas9 and stem cells, hoping to create cells loaded with more than one drug to respond to different triggers of inflammation and treat a variety of chronic diseases and tissue types
.
Reference: [1] Choi, YR, et, al.
(2021).
A genome-engineered bioartificial implant for autoregulated anticytokine drug delivery.
Science Advances, 7(36).
https://doi.
org/10.
1126/sciadv.
abj1414[2] CRISPR-Engineered Cells Release Drug in Response to Inflammation When Implanted into Mice.
Retrieved September 2, 2021, from https:// response-to-inflammation-when-implanted-into-mice/Note: This article aims to introduce the progress of medical and health research, not a treatment plan recommendation
.
If you need guidance on the treatment plan, please go to a regular hospital for treatment
.
.
However, about 40% of RA patients do not respond to treatment, and continuous high-dose administration will suppress the immune system, which may cause serious adverse reactions, such as increasing the risk of infection
.
Recently, scientists have used CRISPR-Cas9 genome editing technology to transform induced pluripotent stem cells (iPSCs)
.
These cells can be implanted subcutaneously.
In the RA mouse model, once inflammation occurs, the implanted "smart" cells will automatically sense the changes in the level of endogenous inflammatory cytokines and respond to deliver a corresponding therapeutic level.
Anti-inflammatory biological products can significantly reduce inflammation and completely prevent bone erosion
.
▲The paper was published in the peer-reviewed journal Science Advances (picture source: screenshot of the paper page) Biological products usually target several inflammatory cytokines and pathways, including interleukin-1 and -6 (IL-1 and IL-6) ), tumor necrosis factor -α (TNF-α) and the like
.
However, over time, the severity of RA disease may fluctuate.
When using these drugs for injection or infusion therapy, regardless of the patient's cytokine level or RA symptoms, they tend to be administered continuously at higher concentrations.
, Leading to adverse reactions
.
Therefore, the development of specific treatment strategies that can sense and respond to the levels of endogenous inflammatory factors is expected to reduce unnecessary side effects when effectively treating patients
.
A research team from Washington University School of Medicine in St.
Louis, USA, used CRISPR-Cas9 genome editing technology to transform induced pluripotent stem cells (iPSCs), and constructed cartilage stem cells (Stem cells) called “SMART”.
Cells Modified for Autonomous Regenerative Therapy), a synthetic gene circuit that is regulated by IL-1 to produce IL-1 receptor antagonist (IL-1Ra) is implanted in the cells
.
IL-1 promotes inflammation of arthritis by activating inflammatory cells in joints
.
When inflammation occurs, the gene circuit in the cell will sense the level of endogenous IL-1 cytokine and be activated to secrete IL-1Ra corresponding to the therapeutic level
.
▲The principle of the treatment plan (picture source: reference [1]) Professor Farshid Guilak, the corresponding author of the paper, explained, “We used CRISPR technology to re-edit the genes in the stem cells, and then by seeding the cells on the braided scaffold, Created a small cartilage implant and placed it under the skin of the mouse
.
This method allows these cells to exist in the body for a long time, and once an inflammatory response occurs, the corresponding proportional drug will be secreted
.
" Interestingly, although IL-1Ra has been proven to improve symptoms in animal models, it is not often used to treat rheumatoid arthritis because of its short half-life and average efficacy
.
However, this innovative self-regulating therapy of stem cells + implanted biological scaffolds overcomes the half-life and curative effects of drugs
.
Researchers found that IL-1Ra drugs significantly reduced joint inflammation and pain in mice
.
Moreover, when using radioactive imaging technology to observe bones, the drug inhibits bone damage commonly seen in rheumatoid arthritis and completely eliminates bone erosion
.
Bone erosion is bone destruction caused by disease deterioration.
Current treatments cannot effectively deal with it.
Therefore, there are important unmet clinical needs
.
Even better, researchers can also use CRISPR-Cas9 gene editing technology to create different types of drugs
.
In other words, if one therapeutic drug works better than another in a particular patient, it may be possible to develop individualized therapies by reprogramming chondrocytes
.
This treatment plan also has great potential to treat other inflammatory arthritis diseases, including juvenile arthritis
.
Researchers are continuing to experiment with CRISPR-Cas9 and stem cells, hoping to create cells loaded with more than one drug to respond to different triggers of inflammation and treat a variety of chronic diseases and tissue types
.
Reference: [1] Choi, YR, et, al.
(2021).
A genome-engineered bioartificial implant for autoregulated anticytokine drug delivery.
Science Advances, 7(36).
https://doi.
org/10.
1126/sciadv.
abj1414[2] CRISPR-Engineered Cells Release Drug in Response to Inflammation When Implanted into Mice.
Retrieved September 2, 2021, from https:// response-to-inflammation-when-implanted-into-mice/Note: This article aims to introduce the progress of medical and health research, not a treatment plan recommendation
.
If you need guidance on the treatment plan, please go to a regular hospital for treatment
.
