Nanoparticles used to deliver CRISPR gene editing tools into the cell

Researchers from Tufts University and the Chinese Academy of Sciences have developed a novel method to effectively deliver the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat (CRISPR) associated protein 9) gene editing tools into the liver for genetic studies.

The team used novel nanoparticles as carriers to do the courier’s job. Their study titled, “Fast and efficient CRISPR/Cas9 genome editing in vivo enabled by bioreducible lipid and messenger RNA nanoparticles”, was published in the latest issue of the journal Advanced Materials.

The large complex of gene editing molecules is difficult to deliver into cells from external an external application. Biodegradable lipid nanoparticles deliver mRNA coding for the gene editing molecules into the cell. Image Credit: From animation by Visual Science and Skoltech (https://visual-science.com/ )
The large complex of gene editing molecules is difficult to deliver into cells from external an external application. Biodegradable lipid nanoparticles deliver mRNA coding for the gene editing molecules into the cell. Image Credit: From animation by Visual Science and Skoltech (https://visual-science.com)

The gene editing tool CRISPR/Cas9 has been one of the path breaking revolutions in gene editing and therapy using genetic modulation. There has been however always the challenge of how to get this mechanism into the cells effectively so that they could perform their appointed tasks. The team of researchers now have used biodegradable synthetic lipid nanoparticles that would help carry the editing tools for the genes into the cell. Now this tool would be used to change the genetic code with more than 90 percent effectiveness. The team of researchers add that these nanoparticles have been proven to be the most effective tool to carry the gene editing technology into the cell. This could be greatly beneficial for many patients who benefit from the therapeutic applications of CRISPR/Cas9 they add.

CRISPR-Cas9 systemibreakstock | Shutterstock

The team writes that this new gene editing tool CRISPR/Cas9 has been a great boon for genetic research as well as providing gene therapy. It has been used successfully to understand the functions and molecular mechanisms of thousands of genes and their role in health and disease. Tweaking genes could be used to treat various disease and are being developed. One of the greatest hurdles in development of therapeutic applications for this gene editing tool is that it is a large molecular complex. It has a nuclease enzyme called the Cas9 that is utilized as scissors to cut through the strands of the genomic sequence. In addition the complex has a “single guide” RNA that has been engineered. It is called the sgRNA. This sgRNA scans the whole of the genetic code using the nuclease and finds the exact region that needs to be cleaved and edited. The whole complex thus is large and bulky and it is difficult to transport it into the living cell nucleus where it can function. There have been studies and attempts where researchers have used various delivery techniques including viruses, different types of nanoparticles, polymers etc. However none of these have provided a high efficiency of transfer so that the technique could be used for clinical therapy in patients.

The researchers for this study used lipid nanoparticles - BAMEA‐O16B. They used these nanoparticles to encapsulate the messenger RNA (mRNA) that could code for the Cas9. The contents of the nanoparticles release the mRNA as well as the sgRNA into the cell. The cell has its own protein making machinery that works to prepare the Cas9 from the mRNA template that is carried into the cell. Thus the Cas9 is ready for use within the cell prepared by the cell itself. Now the gene editing kit is ready, the team explains. The researchers add that these nanoparticles are made of synthetic lipids and contain disulfide bonds in the fatty chain. Once they enter the cell the disulphide bonds break open and now the nanoparticles get disassembled and the contents are released and distributed within the cell.

Qiaobing Xu, co-corresponding author of the study and associate professor of biomedical engineering at Tufts University explained, “We are just starting to see human clinical trials for CRISPR therapies. There are many diseases that have long been intractable for which CRISPR therapies could offer new hope - for example sickle cell disease, Duchenne muscular dystrophy, Huntington's disease, and even many cancers. Our hope is that this advance will take us another step toward making CRISPR an effective and practical approach to treatment.” The study first author was Ji Liu, graduate student from Chinese Academy of Sciences, Institute of Chemistry.

For this study the team of researchers used lab mice and utilized these nanoparticle carriers to tweak and reduce the activity of a gene in the mice coding for the PCSK9. When this gene is lowered, it reduces LDL cholesterol and thus reduce the risk of cardiovascular disease. Results showed that superior efficacy of the gene editing tool when the lipid nanoparticles were used.

Ming Wang, co-corresponding author of the study and professor at the Chinese Academy of Sciences, Beijing National Laboratory for Molecular Science, explained, “The lipid nanoparticles are one of the most efficient CRISPR/Cas9 carriers we have seen. We can actually knock down PCSK9 expression in mice with 80 percent efficiency in the liver, suggesting a real promise for therapeutic applications.”

Authors of the study concluded, “The leading lipid nanoparticle, BAMEA‐O16B, represents one of the most efficient CRISPR/Cas9 delivery nanocarriers reported so far, and it can broaden the therapeutic promise of mRNA and CRISPR/Cas9 technique further.”

The study was funded by National Key Research and Development Program of China and the National Science Foundation of China along with National Institutes of Health.

Journal reference:

Liu, J., Chang, J., Jiang, Y., Meng, X., Sun, T., Mao, L., Xu, Q., Wang, M., Fast and Efficient CRISPR/Cas9 Genome Editing In Vivo Enabled by Bioreducible Lipid and Messenger RNA Nanoparticles. Adv. Mater. 2019, 1902575. https://doi.org/10.1002/adma.201902575, https://onlinelibrary.wiley.com/doi/abs/10.1002/adma.201902575

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Mandal, Ananya. (2023, May 27). Nanoparticles used to deliver CRISPR gene editing tools into the cell. News-Medical. Retrieved on October 10, 2024 from https://www.news-medical.net/news/20190715/Nanoparticles-used-to-deliver-CRISPR-gene-editing-tools-into-the-cell.aspx.

  • MLA

    Mandal, Ananya. "Nanoparticles used to deliver CRISPR gene editing tools into the cell". News-Medical. 10 October 2024. <https://www.news-medical.net/news/20190715/Nanoparticles-used-to-deliver-CRISPR-gene-editing-tools-into-the-cell.aspx>.

  • Chicago

    Mandal, Ananya. "Nanoparticles used to deliver CRISPR gene editing tools into the cell". News-Medical. https://www.news-medical.net/news/20190715/Nanoparticles-used-to-deliver-CRISPR-gene-editing-tools-into-the-cell.aspx. (accessed October 10, 2024).

  • Harvard

    Mandal, Ananya. 2023. Nanoparticles used to deliver CRISPR gene editing tools into the cell. News-Medical, viewed 10 October 2024, https://www.news-medical.net/news/20190715/Nanoparticles-used-to-deliver-CRISPR-gene-editing-tools-into-the-cell.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
New cell therapy offers effective treatment for patients with T-cell acute lymphoblastic leukemia