CRISPR technology’s initial applications were primarily focused on targeted genome editing, but its use has expanded into cell line engineering, which holds promises of groundbreaking advancements, insists Philip Hargreaves.
CRISPR technology has come a long way since its discovery as a natural defence mechanism in bacteria. Scientists have harnessed its potential to precisely edit genes, paving the way for groundbreaking advancements in genetic engineering. Initially, CRISPR was primarily used for editing specific genes within organisms, but its scope has expanded rapidly to include the manipulation of entire cell lines. This ability to edit cell lines using CRISPR technology has unlocked a myriad possibilities.
For many years researchers and drug developers have used immortalised cell lines (derived from humans but engineered to have stable properties over many divisions) to aid their work. These cell lines typically have the gene and/ or protein target of interest expressed within them. CRISPR methodology has allowed quicker and more optimal manipulation of these cell lines.
As of now, CRISPR cell line technology is being used extensively for medical and agricultural applications. In medicine, researchers are employing CRISPR to engineer cell lines for therapeutic purposes, intending to treat diseases at the genetic level. For instance, CRISPR has been used to edit the genes of immune cells, enabling them to better target and eliminate cancer cells.
The future landscape
Looking ahead, the future of CRISPR cell line technology holds even more transformative possibilities. One of the key areas of exploration is regenerative medicine, where researchers aim to harness CRISPR to engineer cells for tissue repair and organ regeneration. The ability to precisely edit and manipulate cell lines could open new avenues for treating degenerative diseases and injuries, potentially revolutionising the field of transplantation.
CRISPR technology is further poised to play a crucial role in the development of novel therapies for genetic disorders. The ability to edit problematic genes could pave the way for more effective treatments and even cures for conditions that were once considered incurable, such as Alzheimer’s.
Despite the remarkable progress in CRISPR technology, challenges and roadblocks still need to be addressed. Off-target effects, unintended mutations and the potential for unpredictable consequences remain significant hurdles in developing and applying CRISPR-based therapies. Researchers are actively working to enhance the precision and safety of CRISPR technology to mitigate these risks.
CRISPR-engineered knock-in cell lines
One way to use CRISPR engineering to generate cell lines, which Promega is successfully offering, is to incorporate HiBiT technology. This 11 amino acid peptide can be fused to a target protein and serves as a luminescent tag. HiBiT can be integrated by knocking in the tag to the endogenous locus of the target using CRISPR gene editing, to help create a truer picture of protein behaviour and regulation in their natural cellular environment.
Widescale adoption and integration of CRISPR cell line technology into various sectors will require collaborative efforts from researchers, policymakers and the private sector
HiBiT has a dynamic range spanning nine logs, which allows for the detection of extremely small quantities of tagged proteins. In terms of applications, HiBiT's versatility is unmatched, as quantitative assays can be performed in both endpoint and live-cell formats, without the need for target-specific antibodies. From measuring target protein abundance to studying targeted protein degradation, protein secretion and receptor recycling, HiBiT opens up a myriad possibilities in biomedical research. Its role in drug discovery is particularly noteworthy, enabling more precise and efficient screening of drug effects on cellular proteins.
The accessibility and affordability of CRISPR technology also need to be addressed to ensure that its benefits are not confined to a privileged few. Widescale adoption and integration of CRISPR cell line technology into various sectors will require collaborative efforts from researchers, policymakers and the private sector. To aid in this endeavour, Promega now offers a comprehensive selection of pre-built CRISPR-edited cell line pools and clones, including HiBiT fusions. This development opens doors for researchers and developers as it reduces the costs involved in developing cell lines from scratch. Not only will this save budgets, but it also saves time. This means drug development times can be reduced by as much as 12 months, leading to vital medications being available much sooner.
Final thoughts
The future of CRISPR cell line technology is undoubtedly exciting and promises transformative advancements in medicine, agriculture, and beyond. As scientists continue to unravel the mysteries of genetic engineering, there is a delicate balance between innovation and ethical stewardship to consider. But with efforts to maximise the technology’s potential to make it more accessible and affordable, the future is bright.
Philip Hargreaves PhD is director of strategic marketing and business development at Promega
