Enhancing Specificity and Delivery in Cancer Treatment: A Study on CRISPR/Cas9 Gene Editing Applications
Today cancer is considered one of the top ten most evil diseases in the world. In earlier days chemotherapy, radiation therapy and surgery were the most orthodox treatments for cancer. Nevertheless, although such procedures have recovered countless lives, they all tend to be harsh and severe in their side effects as well as in their lack of specificity. Not only do they destroy normal cells and tissues, but they also often harm patients ' health and quality of life. The relatively recent advent of the revolutionary technology of CRISPR-Cas9 has created a new era of personalized treatment, especially immunotherapy for cancer. However, it has a restricted range of use because of issues of specificity, off-target effects and target-cell delivery.
The first goal of this study is to develop better accuracy and delivery mechanisms for cancer treatments using the powerful gene editing tool of CRISPR-Cas9. The investigation of new gene-editing technologies and delivery systems aims to lower the risks of current methods and fill an important gap in the application of CRISPR technology in oncology. The second goal is to optimise the delivery system for CRISPR-Cas9 in cancer therapy.
The ultimate objective is to arrive at a more specific, less invasive and immensely more effective cancer treatment regimen. Through improving the accuracy and delivery of CRISPR-Cas9, we aim to give those who suffer from cancer hope in combating this disease with greater precision and fewer side effects.
To improve the specificity of CRISPR-Cas9 in cancer cells
Purpose: Cancer treatment via CRISPR/Cas9 gene editing holds immense promise, yet off-target effects pose a critical challenge, hindering therapeutic precision. This goal aims to find a way to enhance targeting accuracy and eliminate off-target effects.
Method: Two types of analysis will be followed; literature review and experimental study. The literature review will delve into bioinformatics studies, encompassing genome sequencing of diverse cancer cell lines. The goal will be to identify specific genetic aberrations in cancer cells, providing a foundation for precise CRISPR/Cas9 interventions, particularly the precision-cutting capabilities, and gene editing methodologies.
On the other hand, experimental study involves a study of bioinformatics--including the genome sequencing of cancer cell lines, and gene editing using the precision cutting ScisPR-Cas9 method. However, two forms of experimental studies will be undertaken. Firstly, a genome-scale CRISPR/Cas9 loss-of-function screening in cancer cells will be performed using Avana sgRNA library and CERES software. It will aim to assess the impact of gene editing on cancer cell lines.
Secondly, a genome-wide screen to look for genetic dependency in melanoma using a CRISPR-Cas9 approach will be undertaken. This involves using certain equipment and software, like the human Avana4 library for targeting genes to genetic cleanup tool CRISPRcleanR. It will aim to find fitness genes that are specific for melanoma, and the analysis points to useful candidates such as DUSP4 and PPP2R2A which increase when inactivated lower proliferation of melanoma cells. The end goal is to increase the specificity and efficacy in targeted cancer treatment.
Requirement: Familiarity with the concepts and application of gene editing, CRISPR technology, Avana sgRNA library and CERES software is mandatory. This goal also requires advanced-level understanding of molecular biology, bioinformatics, and CRISPR technology
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To optimise delivery systems for CRISPR-Cas9 in cancer therapy
Purpose: The second goal of this research is dedicated to enhancing the effective deployment of CRISPR/Cas9 gene editing in cancer treatment through innovative delivery approaches. It seeks to enhance the delivery of CRISPR-Cas9 to cancer, but reduce systemic exposure. It uses a mix of literature review and experimental study methods. The overall goal is to improve the anti-cancer effectiveness of the treatment and broaden the application of CRISPR/Cas9 in precision cancer therapy.
Methodology: The literature review will explore existing studies on delivery systems, emphasizing non-viral vectors and biopolymers, strengths and limitations in the context of CRISPR/Cas9 therapy. Insights from these investigations will inform the design and selection of optimal delivery platforms for subsequent experiments.
In the first experimental approach, a multifunctional non-viral vector will be engineered for CRISPR/Cas9 delivery, specifically targeting the MTH1 gene for non-small cell lung cancer therapy. The goal is to assess the vector's efficacy in gene editing and its therapeutic impact on cancer cells. The second experiment involves the utilization of a biopolymer (LBP), derived from lactose, as a delivery platform for CRISPR/Cas9 in treating hepatocellular carcinoma. It will use gene editing efficiency and cancer cell proliferation to enhance in-vivo delivery of CRISPR/Cas9 technology for hepatocellular carcinoma. The goal is to develop nanocarrier technologies that accurately and effectively deliver CRISPR components directly to the tumors.
Requirement: Familiarity with the concepts and application of gene editing, gene therapy, nanotechnology, pharmacology, CRISPR/ Cas9 technology.
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There are no completed milestones.