Nov 24, 2021
Marwan Alsarraj is the biopharma segment manager at Bio-Rad. He has been at the forefront of developing, marketing, and commercializing technologies for the past 15 years in the life science research industry. Marwan obtained his MS in biology at the University of Texas, El Paso.
CRISPR-Cas (CRISPR) is a cutting-edge tool for gene editing that has propelled a revolution in the biomedical world—even garnering the 2020 Nobel Prize in Chemistry. Not to mention expedient adoption across research labs worldwide within just a few years.
Many of us—inside and outside of the scientific community—are familiar with CRISPR. Adapted from a naturally occurring genome editing system in bacteria, CRISPR makes it easy to disrupt a targeted gene or insert a new sequence at the precise spot desired if a DNA template is added to the mix. The method has profoundly changed biomedical research, and it has therapeutic gene editing applications, such as improving the safety and efficacy of CAR T immunotherapies.
On the other hand, limitations of this method include a finite ability to modify large numbers of adult cells and the need for a delivery system. Viral vectors are the most common delivery method, but they reintroduce toxicity concerns.
Addressing the limitations of CRIPSR-based systems
Fortunately, CRISPR is not alone. This remarkable tool is thought to be related to transposons: ancient DNA constructs that can jump through DNA via a variety of mechanisms. Transposons also have therapeutic applications, some of which address the limitations of CRISPR-based systems.
Scientists have leveraged transposons for CAR T manufacturing and other types of gene therapy. These alternative approaches have the potential to make DNA editing easier, cheaper, and safer. Transposons more readily cross the cell’s plasma membrane, meaning that they require less-harsh gene delivery systems to enter cells, which improves the therapeutic safety profile. They are simple segments of DNA that can be designed and amplified faster and at a fraction of the cost than it takes to amplify the viral vectors of other systems. Like CRISPR, some transposon systems may be targeted to integrate the therapeutic gene into an optimal location in the genome.
There are benefits and limitations for all gene editing systems. It is important that researchers carefully weigh the merits of each to select a method that best suits their needs. No system is 100 percent efficient or accurate, so for all therapeutics that use gene editing, developers must incorporate strict quality control measures to detect “off-target” edits and accurately measure gene copy numbers to ensure that patients receive the correct transgene at the right dose.
The future is bright
Advancements in genome editing techniques have expanded what scientists can do to address issues facing the pharmaceutical industry and beyond.
While CRISPR has completely revolutionized what genome editing can mean for our future by increasing the speed and breadth of science, the limitations it poses lead any open-minded and thorough scientist to explore the benefits of the other methods available.
We are already experiencing the impact of available genome edition techniques and their role in cell and gene therapies. The future is bright and full of potential across the types of new developments, discoveries, and applications we may see come to fruition as a result.