The CRISPR Horizon: Envisioning the Future of Genomic Editing

31 May 2024

8 Min Read

Associate Professor Dr Yap Wei Hsum (Academic Contributor), Associate Professor Dr Looi Chung Yeng (Academic Contributor), The Taylor's Team (Editor)

IN THIS ARTICLE

Imagine a world where diseases like cystic fibrosis, which affects tens of thousands globally each year, could be cured at the genetic level. Recent scientific breakthroughs in genome editing offer a glimpse into such a future. At the heart of these advances is CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), a tool that not only promises to revolutionise biological research but also carries the potential to fundamentally alter our approach to genetic disorders, agriculture, and environmental management.

Genome editing, facilitated by technologies like CRISPR, involves precisely altering the DNA of a cell or organism to achieve specific outcomes—be it correcting the defective gene responsible for cystic fibrosis or enhancing crop resilience against climate change. As we stand at the threshold of this new era, CRISPR offers extraordinary possibilities to reshape our world. Yet, it also challenges us to consider the ethical dimensions of such power: How do we navigate the fine line between innovation and the natural order? This technology opens doors to unparallelled advancements while urging us to reflect on our responsibilities and the goals we aim to achieve through such profound capabilities.

From Zinc Fingers to TALENs to CRISPR

The narrative of genome editing unfolds with pivotal developments in the late 20th century, laying the groundwork for today’s technologies. In the 1980s, the discovery of zinc finger proteins as DNA (Deoxyribonucleic acid)-binding motifs spearheaded a new era of genetic engineering. By the late 1990s, researchers such as Srinivasan Chandrasegaran, Young Gi Kim, and Jumin Cha had taken a significant leap by merging a zinc finger DNA-binding domain with a DNA-cleavage domain to forge zinc finger nucleases (ZFNs). This was followed by the advent of TALENs (transcription activator-like effector nucleases) in the early 2000s, developed by scientists like Adam Bogdanove and Daniel Voytas. These nucleases offered enhanced specificity and efficiency in targeting genomic sequences. However, the complexity and high costs associated with ZFNs and TALENs restricted their widespread use in research and therapeutic contexts.

Zinc Fingers (noun)

These are special protein structures that can attach to DNA, helping to control which genes are turned on or off. Think of them as tiny ‘fingers’ that can grab onto specific parts of our genetic code. They play an important role in many biological processes and are even used in genetic engineering to make precise changes to DNA.

TALENs (noun)

TALENs are special proteins used to edit genes. They work like molecular scissors, cutting DNA at specific locations so scientists can add, remove, or change pieces of the genetic code. This technology helps researchers understand how genes work and can be used to develop new treatments for genetic diseases.

The transformative breakthrough in genome editing emerged with the discovery of CRISPR-Cas9. Originating as a component of bacterial immune defence, the CRISPR system, along with the Cas9 enzyme, was repurposed for genome editing by Jennifer Doudna and Emmanuelle Charpentier, who published their landmark findings in 2012. Unlike its predecessors, CRISPR-Cas9 utilises a guide RNA (Ribonucleic acid) to direct the Cas9 enzyme to a specific genetic location, performing precise cuts with remarkable ease and efficiency. This method not only simplified the editing process but also made it more accessible and affordable, democratising genome editing across global laboratories.

In 2016, the evolution of CRISPR technology continued with the introduction of base editing by David Liu’s lab at Harvard University. This innovative technique allows for the direct conversion of one DNA base into another without severing both strands of the DNA helix, thereby minimising the risk of undesirable mutations. Base editing has further refined the precision of genomic alterations, promising revolutionary applications in human health and agriculture.

Abstract vector background depicting genetic engineering DNA concept.

Milestones in CRISPR Development

The journey of CRISPR technology from its conceptualisation to its current state has been marked by numerous milestones that highlight its growing impact across various fields. After its initial breakthrough, which repurposed a natural bacterial defence mechanism into a tool for genomic editing, CRISPR has seen a series of rapid advancements that have significantly broadened its applicability and efficiency.

One of the more recent significant advancements is the development of CRISPR-Cas12 and CRISPR-Cas13 systems, which offer different functionalities compared to the traditional CRISPR-Cas9. Cas12 has been noted for its ability to make precise cuts in double-stranded DNA but with added capabilities such as temperature tolerance and target range, enhancing its utility in complex genomic locations. Cas13, on the other hand, targets RNA, providing new avenues for tackling viruses and other pathogens without altering the DNA.

Another milestone was achieved with the advent of ‘CRISPRoff,’ a technology developed by researchers at the University of California, San Francisco. This innovative method allows scientists to turn off almost any gene in human cells without making a single cut in the DNA. Such a capability is crucial for studying disease development and could be instrumental in therapies where permanent gene editing is unnecessary or too risky.

In terms of therapeutic applications, 2020 marked a pivotal year when Victoria Gray became the first person in the U.S. to be treated with a CRISPR-based therapy for sickle cell disease. This treatment, which involves editing the stem cells to produce a modified form of haemoglobin that combats the effects of the disease, has shown promising results, highlighting CRISPR’s potential in treating genetic disorders.

Sickle Cell Disease (noun)

This is a genetic condition affecting the red blood cells, which are crucial for transporting oxygen throughout the body. In sickle cell disease, these cells morph into a stiff, sickle shape, resembling a farmer's crescent-shaped tool. This abnormal shape can cause the cells to clog blood vessels, leading to painful blockages and a shortage of oxygen to body tissues. This condition can trigger severe pain, frequent infections, and potential damage to organs. Sickle cell disease is inherited from one's parents and predominantly occurs in individuals of African, Mediterranean, Middle Eastern, and Indian ancestry.

Transformative Applications of CRISPR

The implications of CRISPR technology extend far beyond the laboratory, promising transformative changes across multiple sectors. Its precision and versatility enable not only the correction of genetic defects but also the enhancement of agricultural productivity and the management of ecosystems, amongst other applications.

Medical Innovations: CRISPR continues to redefine the boundaries of medical science. Beyond ongoing trials for diseases like Duchenne Muscular Dystrophy (DMD) and cystic fibrosis, recent developments have showcased its potential in tackling complex conditions such as Huntington's disease and certain forms of congenital blindness. For instance, a groundbreaking clinical trial in 2021 demonstrated the use of CRISPR to directly edit genes inside the human body for the first time, targeting a rare form of inherited blindness. Additionally, research into using CRISPR-modified T-cells for more personalised and effective cancer immunotherapy has shown promising results, potentially leading to new cancer treatments that are less invasive and more targeted.

DNA sequencing gel run science and data genomic genetic analysis background abstract pattern.

Agricultural Breakthroughs: In agriculture, CRISPR is not just enhancing crop resilience but also accelerating the development of nutritionally enhanced food products. Recent advancements include the engineering of gluten-free wheat and tomatoes with altered levels of growth-inhibiting compounds to extend shelf life and increase yield. These innovations not only promise to improve food security but also cater to specific dietary needs and preferences, marking a significant step forward in agricultural biotechnology.

Agronomist applying fertilizer on plants

Environmental Conservation: CRISPR's role in environmental conservation has expanded to include not only the control of invasive species but also the restoration of habitats through the resurrection of extinct Woolly Mammoth and the fortification of coral reefs against bleaching. Innovative applications, such as the development of gene drive systems to restore balance in ecosystems by selectively breeding resistant species, are currently being tested, which could dramatically alter conservation strategies globally.

Biotechnology and Synthetic Biology: Beyond traditional applications, CRISPR is catalysing advances in synthetic biology, where it is used for de novo biosynthesis of metabolites and reprogramme cellular functions. Recent applications include the development of microbial factories using CRISPR-engineered cells to produce biofuels and bioplastics, reducing reliance on fossil fuels and decreasing plastic pollution.

CRISPR and the Future of Human Potential

The potential applications of CRISPR and base editing extend far beyond treating genetic disorders, venturing into the realms of enhancing human capabilities such as intelligence, physical endurance, and lifespan. This expansion raises exciting possibilities alongside profound ethical questions.

Research on intelligence enhancement through gene editing has begun to target genes associated with neural development. For instance, experiments modifying the NR2B gene in mice, which is known to affect memory and learning, have shown promising results in enhancing these cognitive traits.

In the realm of physical abilities, scientists have explored the manipulation of the myostatin gene, which regulates muscle growth. By inhibiting this gene in animals, researchers have significantly increased muscle mass and strength, initially aiming to treat muscle degeneration diseases.

Perhaps one of the most ambitious potential applications of genomic editing lies in extending human lifespan. Ongoing studies targeting genes like FOXO3, known to influence longevity, explore how genetic manipulation might extend healthy lifespans.

Dr Yap and Dr Looi

In the next decade, CRISPR can drive breakthroughs in modification of immune cells to better target and kill cancer cells, leading to more effective cancer immunotherapy. CRISPR will also enable the development of crops that are more resistant to pests, diseases, and environmental stresses.

AP Dr Yap Wei Hsum and AP Dr Looi Chung Yeng

School of Biosciences

Ethical and Societal Dimensions of Human Genomic Editing

The ethical landscape of human genomic editing is replete with complexities and profound moral questions. As technology enables the editing of genes to enhance traits like intelligence or physical strength, society faces the daunting prospect of 'playing God' with human biology. These capabilities not only ignite debates over the moral implications but also spotlight the potential misuse of such technology, as exemplified by the controversial case of gene-edited babies in China.

The possibility of genetic enhancements becoming luxury goods accessible only to the affluent is a pressing concern. Such a scenario risks deepening existing inequalities in healthcare access and other essential services. This disparity prompts critical societal questions: How will we bridge the gap between those who can afford genetic enhancements and those who cannot? What long-term impacts might this have on social stratification and opportunity access?

Moreover, genetic enhancements carry the risk of unintended consequences—unpredictable alterations that could irreversibly change the human gene pool and be passed down through generations. These enhancements could profoundly reshape core human experiences and societal values, potentially redefining concepts of merit traditionally associated with natural talent and hard work. As these technologies become more widespread, they may fundamentally alter how achievements are valued, particularly in competitive environments like schools and workplaces.

Drone Point View of Overpass and City Traffic at Night / Beijing, China

The pressure to undergo genetic enhancements to remain competitive could raise serious ethical concerns about autonomy and consent. Individuals might feel compelled to seek genetic modifications, not out of desire, but out of necessity to uphold a standard in their professional and personal lives. Such pressures could have deep psychological impacts and alter one's sense of identity. In response, there might be calls for regulatory frameworks that ensure enhancements are used ethically and equitably, potentially by establishing a baseline for 'enhancement equality' akin to principles in disability rights and access.

Furthermore, if genetic enhancements remain exclusive to wealthier segments of society, this could create a divide between the genetic 'haves' and 'have-nots.' To prevent such social divisions, governments and international bodies might consider policies similar to those for healthcare, ensuring equitable access to genetic enhancements through subsidies or public funding.

The long-term implications for human evolution are significant. Selectively amplifying traits through genetic enhancements could diminish human diversity, which has historically been a source of resilience and adaptation. It is crucial to maintain this diversity to avert unforeseen consequences in our gene pool. Policymakers might need to intervene to preserve a range of genetic variations, mirroring efforts in biodiversity conservation.

As we advance with genome editing technologies, we are challenged to reconsider the intersection of technology, ethics, and society. Engaging in robust dialogues and thoughtful policymaking will be crucial to navigating these new ethical, cultural, and social terrains. The pivotal question remains: How can we ensure these powerful technologies benefit all without compromising our fundamental values?

Conclusion

As we explore the profound capabilities of genomic editing, we stand at a crossroads that will define the future of humanity. The advancements in this field promise unparallelled opportunities to enhance human life, eradicate diseases, and extend our biological limits. Yet, these possibilities also come with significant ethical, societal, and philosophical challenges that must be carefully navigated.

The journey of genomic editing is not just a scientific endeavour but a societal one that requires a collective reflection on what it means to be human in an era of technological transcendence. As we consider the potential to reshape human abilities and destinies, we must also prioritise equity, consent, and the preservation of human diversity. The balance between technological advancement and ethical responsibility will be crucial in ensuring that genomic editing benefits all of humanity without compromising the values we cherish.

Ready to redefine the future? Discover how you can pioneer groundbreaking advancements in CRISPR and genetic engineering with our Bachelor of Biotechnology and Bachelor of Biomedical Science programmes. Don’t just dream about making a difference—make it your career! Book an appointment with our education counsellors today to explore the endless possibilities.

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