Changes in the Genome
[Alaina Rumrill] Dr. Bomyi Lim, a distinguished Professor of Chemical and Biomolecular Engineering at the University of Pennsylvania, has made significant strides in understanding gene expression and the role of epigenetic markers [1]. After completing her undergraduate and doctoral studies in chemical and biological engineering at the University of Pennsylvania and Princeton University, Dr. Lim advanced her knowledge as a research fellow at Princeton’s Genomics Institute [1]. Here, she explored how chemical engineering principles can be applied to biological systems, under the influence of a Ph.D. advisor focused on gene expression mechanisms. These early experiences inspired her to investigate how changes within the genome affect gene expression and biological function, ultimately leading her to focus on epigenetics, the study of heritable changes in gene expression that do not alter the underlying DNA sequence [1].
In her current work, Dr. Lim emphasizes two main types of genome modifications: nucleotide editing and chemical modifications to the genome, such as acetylation and methylation [1]. These modifications, while nuanced, have a substantial impact on how genes are expressed without permanently altering the DNA sequence itself [1]. Acetylation, for instance, generally promotes gene expression by loosening DNA structure, making it more accessible, while methylation tends to suppress gene activity, effectively silencing specific genes [2]. Dr. Lim’s approach to this research is particularly systematic and strategic. Through synthetic biology and mathematical modeling, she is working on ways to reverse or prevent moderate changes to the genome by precisely targeting specific epigenetic markers [1]. Her focus on moderate genome changes is motivated by their potential to offer controlled solutions for treating diseases and understanding complex biological functions without permanently altering the DNA.
Dr. Lim’s research holds vast implications for our understanding of human development, metabolism, and disease. Advances in the ability to control gene expression through reversible epigenetic changes offer a groundbreaking alternative to traditional therapies. This approach could lead to treatments that manage genetic predispositions or minimize disease risk by adjusting gene activity in a targeted, non-permanent way [1].
CRISPR and Gene Editing
A major area of Dr. Lim’s research involves CRISPR technology, which stands at the forefront of gene-editing tools. CRISPR, often described as “molecular scissors,” allows scientists to precisely edit genes by targeting specific DNA sequences with the Cas9 enzyme [3]. Dr. Lim’s work focuses on refining this process, making it a powerful tool for clinical applications. Her research has demonstrated how CRISPR can be used in clinical trials, particularly for conditions such as sickle cell anemia and beta-thalassemia [1]. In these trials, CRISPR technology has shown promising results, with patients experiencing significant improvements and, in some cases, nearing approval for prescription therapy [1].
Dr. Lim’s CRISPR research is driven by the potential of gene therapy to revolutionize medicine. By editing somatic cells—cells that do not pass genetic information to offspring—scientists can treat patients without affecting future generations [1]. For example, CRISPR-edited somatic cells can address genetic disorders in affected individuals without altering their reproductive cells. However, Dr. Lim acknowledges the challenges associated with CRISPR, including potential off-target effects [1]. These unintended edits can disrupt non-target genes, leading to unexpected outcomes. To address this, her team is working to refine CRISPR methods to enhance precision, reduce off-target impacts, and minimize the chances of accidental gene modification [1].
Beyond technical concerns, Dr. Lim remains attentive to the ethical implications of CRISPR and gene editing. Her research touches on the growing debate over the permissibility of gene alteration, particularly concerning non-somatic, or germline cells, which would pass edits to future generations [1]. Editing germline cells brings significant ethical challenges, as these modifications carry permanent, inheritable consequences that impact descendants. Dr. Lim advocates for careful consideration of both societal and individual implications, stressing that scientific responsibility is paramount when working with gene-editing technologies as powerful and consequential as CRISPR [1].
Scientific Perspective on Human Genetic Modification
Dr. Lim’s insights into gene editing and epigenetic research led her to a measured perspective on human genetic modification, especially when it involves editing embryos. With advancements in CRISPR and other gene-editing technologies, the potential to alter human embryos has moved from a theoretical possibility to a contentious ethical issue. Dr. Lim views human embryo editing as a sensitive and ethically complex area, given the potential for permanent changes to the human genome [1]. Public reaction to embryo editing has been polarized, especially following the controversial use of CRISPR in human embryos in 2018, which resulted in widespread ethical concerns and regulatory responses worldwide [1].
Dr. Lim acknowledges the historical precedents that have shaped public discourse around genetic modification. The cloning of Dolly the sheep, for instance, first sparked questions about the moral and ethical boundaries of genetic manipulation [4]. Similarly, the editing of human embryos has reignited concerns about the implications of making irreversible changes to the human genome. For Dr. Lim, these precedents underscore the need for stringent ethical guidelines and thorough public discussion before any application of gene editing in embryos is considered permissible [1]. She emphasizes that the scientific community bears a responsibility to ensure that advancements are made with a commitment to transparency, ethics, and the well-being of both current and future generations [1].
For Dr. Lim, balancing the potential risks and benefits of gene editing is essential. She believes in the importance of public understanding and awareness, as informed discussions can promote a healthy discourse on this rapidly evolving field [1]. Dr. Lim supports efforts to make gene-editing information more accessible, encouraging scientists, policymakers, and the public to participate in conferences, symposiums, and open discussions that address the ethical, social, and practical implications of these technologies [1]. Looking forward, Dr. Lim envisions a world where gene-editing advances benefit human health without compromising ethical principles. Her work serves as a testament to the importance of scientific responsibility in an era of unprecedented technological possibility, reminding us of the profound impact of our choices on future generations [1].
Learn More
If you would like to hear more about Dr. Bomyi Lim’s journey and work on the regulation of chemical kinetics in biological systems, visit us on Spotify, Apple Podcasts, and many other streaming services to listen to our ChemTalk Podcast with Dr. Bomyi Lim, Professor of Chemical and Biomolecular Engineering at the University of Pennsylvania.
Find the ChemTalk podcast here.
Works Cited
[1] Lim, Bomyi. Personal interview. Conducted by Erin Suh and Alexander Seo. 11 February 2024.
[2] Miller, Jaime L, and Patrick A Grant. “The Role of DNA Methylation and Histone Modifications in Transcriptional Regulation in Humans.” Sub-cellular biochemistry, 2013. https://pmc.ncbi.nlm.nih.gov/articles/PMC6611551 .
[3] science, Wellcome connecting. “What Is CRISPR-Cas9?” new_your_genome. Accessed October 27, 2024. https://www.yourgenome.org/theme/what-is-crispr-cas9/#:~:text=The%20CRISPR%2DCas9%20system%20consists,then%20be%20added%20or%20removed .
[4] “How Dolly the Sheep Sparked Debate over Cloning.” History.com, September 25, 2024. https://www.history.com/news/dolly-the-sheep-cloning .