Transforming the process of drug discovery using CRISPR
The process of drug discovery involves discovery and development of new drug candidate by screening and evaluation of chemical compounds for therapeutic use. This results in safe and effective therapy for various diseases. But this process of discovery, analysis, and testing the candidate drug is challenging, time-consuming, and costly. Besides, only a few drug candidates make their way to market. These barriers can be removed using new technology like CRISPR.
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. CRISPR is used as gene-editing technology that allows to precisely modify a piece of DNA sequence in the genome of any organism. These repeats are mainly found in bacteria’s DNA which act as their immunity. It comprises only a nuclease which is often CRISPR-associated protein Cas-9 and a guide RNA (g-RNA).
Application of CRISPR in the main four stages of drug discovery process
Target identification
The first step in drug discovery is identification of drug target associated with the disease of interest. High-throughput genomics screening using CRISPR provides affordable access to large numbers of drug targets, advancing the search for potential candidates. It also helps in unravelling new drug targets to establish a strong relationship between targets and diseases. Once a recognized target is identified, further functional information is collected through in vitro and in vivo studies. CRISPR may support in these processes by smooth gene knockouts or protein overexpression in cell lines.
Compound screening
The next step in drug discovery is to scan millions of compounds using high-throughput screening. Using CRISPR, it can generate better cellular models to perform high-throughput screening of compounds, which can help to identify the most effective drug molecule for the therapeutics. This could transform drug designing, save time, reduce cost, and accelerate the process of drug discovery.
Hits validation
Hit molecules identified through CRISPR-based screening process are validated through various cell-based assays. CRISPR can validate rapid and generate economical model through accurate genome editing. It can allow to produce cell lines with genetic background related to disease of interest, which can help improve the efficacy of hits validation. Also, it can help in accurate assessment of potential drugs for therapeutic benefits.
Lead optimization
The hit validation process narrow down thousands of hits to some lead compounds that are optimized and further tested for safety. This is the most important step, which includes synthesis of the lead molecule, decreased off-target activities, improved potency, increased chemical stability, and less toxicity. CRISPR can speed up the lead optimization through generation of cellular and animal models for specific human disease condition, which can evaluate the efficacy and safety of drug candidate.
CRISPR technology can build a platform to develop next-generation therapeutics. It also provide hopes for developing faster therapeutics that can contribute towards advances in precision therapeutics. It can also help in finding more drugs for the diseases like cancer and may save many lives through the research it enables. Therefore, CRISPR technology provides an important tool in drug discovery and this will make the way for better and safer therapeutics.
