Introduction to CRISPR: An Advancement in Gene-Editing Technology

CRISPR, the gene-editing technology, has witnessed rapid advancements. Its capabilities have expanded from basic gene editing to adding genes, disabling harmful genes, replacing DNA units, and even altering the genetic makeup of an entire species permanently. Recently, there is a breakthrough as scientists at Massachusetts Institute of Technology (MIT) have re-engineered CRISPR to manipulate single units in RNA, molecules crucial to the encoding of genetic information.

The Role of RNA in Gene Alteration

RNA are the messengers carrying DNA information to protein-generating sections of a cell. Without RNA, the majority of DNA's coding becomes virtually irrelevant. Essentially, RNA is analogous to a computer program assembler that compiles software code into an executable program. The study led by Dr. Feng Zhang, a trailblazer in understanding the immense editing potential of CRISPR in mammalian cells, is shaping a tool called RESCUE, which is designed to replace RNA units.

RESCUE: A Tool to Transpose RNA Units

RESCUE is an improvement over Dr. Zhang's initial efforts aimed at swapping one RNA unit for another. It can now swap two pairs of units simultaneously, doubling the ability to counter disease-causing mutations conveyed by RNA. Moreover, the tool facilitates the modification of how molecules in our cells interpret and relay information. This allows scientists to manipulate the processes governing cancer cell growth or neuron mortality from Alzheimer's and other diseases.

Rising Prominence of RNA in Biomedicine

RNA function as a simplified representation of DNA. When a gene dispatches its message, it instructs the assembly of short RNA strands that capture the coding information necessary to generate a protein. RNA's significance has surged as its manipulation allows for the control of gene expression. In 2018, the FDA endorsed the first RNA targeting gene silencing drug. Amid the growing popularity of DNA concentrated CRISPR, targeting RNA remains a prime objective for three key reasons: it permits temporary gene therapy, yields similar results to genome editing without the associated risks, and allows the modification of vital protein areas.

RNA Editing with CRISPR

RNA editing with CRISPR presents a simple, sturdy, and effective method to intervene in critical biological processes. Dr. Zhang's team discovered the first CRISPR variant, REPAIR, that could edit RNA units in 2017. To generate REPAIR, the team linked the CRISPR family scissor protein, Cas13, with ADAR2, a protein that initiated the replacement of one RNA unit with another.

The RESCUE System

The new system, RESCUE, leverages REPAIR as a framework. Using a selective evolution process, the team obtained a RESCUE construct with an editing efficiency of up to 80%. It has many clinical applications, such as altering the growth patterns of cells similar to those found in prostate and other cancers, making it a significant development within the field.

Challenges and Future Outlook

While RESCUE merges the benefits of RNA editing with CRISPR's potential, it is not without challenges. Its efficacy and specificity require more refining for clinical use. Moreover, the temporary effects of editing due to RNA regeneration may pose challenges when combating a lifelong genetic disease. Despite these challenges, the applications of the CRISPR system to RNA are rapidly expanding. Dr. Gene Yeo's efforts to create a startup that uses CRISPR to target and degrade RNA for incurable conditions such as Huntington's disease hints towards a promising future for RNA-focused gene-editing therapies.

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