CRISPR-Cas9’s Gene Editing Potential in Cancer Therapy

Toxicity resulting from cancer therapy is usually the result of the repeated administration of cancer drugs. On the other hand, the efficacy of CRISPR-Cas9 has been largely affected by problematic editing due to the large size of Cas9’s nuclease and the toxicity of delivery systems.

A recent article in Science Advances discusses the improved delivery system of genome editing in two incurable cancers in mice, and it will be examined in this article.

Researchers have now tested a non-viral lipid nanoparticle (LNP) system designed for CRISPR-Cas9 gene editing. The system successfully edited up to ninety-eight percent in various cancer cell types in the laboratory, and gene editing of approximately eighty percent in live organisms.

A Safe and Efficient Delivery System

In the latest effort to provide safe and efficient delivery of Cas9 sgRNA (single guide RNA) and Cas9 mRNAs (messenger RNAs), scientists have designed LNPs that use ionizable cationic lipids. The LNPs are at the top of the list of applications for small interfering RNA (siRNA) delivery in liver disease. Yet their role in cytoplasmic material (existing outside of the nucleus) has yet to be determined.

A recent report on siRNA encapsulated LNPs describes the treatment of difficult to manage (intractable) cancers, inflammatory neurological disorders, viral infections, and genetic diseases. Almost any disease can be treated through the silencing of a disease-causing mutation or editing defective genes.

However, sophisticated delivery systems are required to deliver macromolecules to the target cell’s interior. Effective LNP-based delivery systems for siRNA that contain ionizable cationic lipids show promise and are the leading candidates. The improvements include reduced immune responses, flexibility of design, ease of manufacturing as well as multi dosing capabilities.

Early Results

LPN, composed of ionizable cationic lipids (ICLs) are now the foremost systems for siRNA delivery in liver disorders. ICLs are of critical importance in LNP stability and structure. Yet their participation in cytoplasmic (a cell’s semifluid substance) delivery has yet to be deciphered.

Orthotopic Glioblastoma

An intracerebral injection of CRISPR-LNPs into orthotopic glioblastoma facilitated approximately seventy percent gene editing against Polo-like kinase 1 (Plk1). Plk1 is a mitotic (relating to cell division) biological regulator that has a wide range of functions continuously identified in the cell cycle. Tumor cell death (apoptosis), decreased tumor growth by fifty percent, and survival was improved by thirty percent.

About Targeting Strategy

The first targeting strategy was designed using the ASSET linker system. At this point in time, it is believed to be the only example of CRISPR-Cas9 gene editing designed to treat metastatic tumors. By targeting, the limitations of most nanoparticle delivery systems and LNPs can be overcome. The therapeutic effect of these systems is mostly confined to the liver and various central organs. In addition, targeted LNPs can target disseminated and localized cells.

The full article is available here.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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