Week 1 HW: Principles and Practices
From Genes to Neurons : CRISPR as a Breakthrough for Ischemic Stroke
- Describe a biological engineering application or tool you want to develop and why?
Stroke, or cerebrovascular accident (CVA), is a leading cause of mortality and morbidity in my country, Indonesia. Compared to other Southeast Asian countries, Indonesia has the highest age- and sex-standardized mortality rate and the greatest loss of disability-adjusted life years. Reducing stroke incidence is key to lowering stroke-related disability. This condition is generally classified as either ischemic—caused by arterial blockage from thrombi, emboli, or hemorrhagic, due to intracranial bleeding. Ischemic stroke, the most common type, often stems from atherosclerosis or thromboembolism. Given these issues, I want to learn more about the problem and what solutions we can develop through biological engineering. Despite advances in acute management, current therapeutic options remain limited, highlighting the need for innovative strategies. In this context, CRISPR genome-editing technology has emerged as a promising biological engineering approach, offering the potential to modulate genes involved in inflammation, neuroprotection, and vascular repair, thereby opening new avenues for ischemic stroke research and therapy.
- Describe one or more governance/policy goals related to ensuring that this application or tool contributes to an “ethical” future, like ensuring non-malfeasance (preventing harm). Break big goals down into two or more specific sub-goals.
A primary governance goal is to ensure non-malfeasance by preventing unintended harm from CRISPR applications in ischemic stroke therapy, such as off-target genetic edits or exacerbation of inflammation. Mandate preclinical trials with multi-generational follow-up to verify no adverse effects on edited genes, restricting use to well-characterized targets prevalent in healthy populations. Besides that, establish regulatory for ongoing risk reassessment, prohibiting germline editing until credible data confirm safety and barring enhancements beyond disease prevention.
- Describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”).
Establish Multidisciplinary Oversight Committees
The purpose to ensure ethical oversight of CRISPR applications in stroke therapy by balancing innovation with bioethics principles like non-maleficence and justice. Form committees with clinicians, geneticists, ethicists, policymakers, and patients to review protocols, informed consent, and long-term follow-ups before clinical trials. Risks of Failure -> Oversight committees may slow down research due to bureaucratic delays, suffer from unequal influence among members, or lack up-to-date technical expertise in CRISPR. If their decisions are not enforceable, the committees may have little real impact beyond symbolic approval. Success -> This action succeeds if it ensures ethical, transparent, and inclusive decision-making for CRISPR stroke therapies, strengthens patient safety and informed consent, and builds public trust while still allowing responsible scientific innovation.
Implement Transparent Global Reporting Standards
The purpose to promote equity and prevent misuse by mandating open data on CRISPR stroke trials, aligning with frameworks like WHO’s genome editing guidelines. This governance require public registries for trial data, adverse events, and equity metrics, audited by independent bodies like NExTRAC (Novel and Exceptional Technology and Research Advisory Committee) equivalents. International cooperation overcomes data-sharing barriers digital platforms ensure accessibility. Risks of Failure -> Data suppression by proprietary interests; overload of unverified info eroding trust. Success -> Accelerated learning from global trials, reducing disparities in stroke therapy access.
Mandate Risk-Based Preclinical Testing Protocols
The purpose is to prevent harm from off-target edits or unforeseen effects in ischemic stroke gene therapies by enforcing rigorous safety validation. This governance require multi-generational animal studies, off-target analysis, and delivery system testing (e.g., nanoparticles for brain access), with phased human trials tied to milestones. Besides that, current lab tech accurately predicts human outcomes; funding supports extended testing timelines. Risks of Failure -> High costs exclude smaller researchers; false negatives allow subtle long-term harms. Success -> Proven safety data enabling equitable regulatory approval in high-burden areas like Indonesia.
- Score (from 1-3 with, 1 as the best, or n/a) each of your governance actions against your rubric of policy goals. Establish Multidisciplinary Oversight Committees (A) Implement Transparent Global Reporting Standards (B) Mandate Risk-Based Preclinical Testing Protocols (C)
| Does the option: | Option 1 (A) | Option 2 (B) | Option 3 (C) |
|---|---|---|---|
| Enhance Biosecurity | |||
| • By preventing incidents | 1 | 1 | 1 |
| • By helping respond | 2 | 2 | 2 |
| Foster Lab Safety | |||
| • By preventing incident | 1 | 1 | 1 |
| • By helping respond | 2 | 2 | 2 |
| Protect the environment | |||
| • By preventing incidents | 2 | 1 | 3 |
| • By helping respond | 2 | 2 | 2 |
| Other considerations | |||
| • Minimizing costs and burdens to stakeholders | 3 | 2 | 1 |
| • Feasibility? | 2 | 1 | 1 |
| • Not impede research | 3 | 1 | 1 |
| • Promote constructive applications | 2 | 1 | 2 |
| • Patient safety and clinical risk | 1 | 1 | 3 |
| • Ethical acceptability | 1 | 2 | 3 |
| • Scientific effectiveness | 2 | 1 | 2 |
| • Equity and access | 2 | 1 | 3 |
| • Long term sustainability | 2 | 1 | 3 |
- Drawing upon this scoring, describe which governance option, or combination of options, you would prioritize, and why. Outline any trade-offs you considered as well as assumptions and uncertainties.
Drawing on the scoring across safety, feasibility, and responsible innovation criteria, I would prioritize a combination of Option 2 and Option 1. This hybrid approach best balances patient safety, ethical responsibility, and scientific progress in the development of CRISPR based therapies for stroke. The main trade-off in prioritizing this combined approach is speed versus safety. Centralized oversight may slow research timelines and increase administrative burdens for researchers and institutions. However, these costs are justified by the high clinical risks associated with CRISPR, including off-target effects, long-term genomic consequences, and unequal access if therapies are commercialized too quickly. In contrast, a minimally regulated, market-driven approach was not prioritized due to its poor performance in patient safety, ethical acceptability, and equity.
JOURNAL SOURCE : Adityasiwi, G.L., Budiono, I., Zainafree, I., Cahyati, W.H. 2025.Stroke in Indonesia: An epidemiological overview. Physical Therapy Journal of Indonesia 6(1): 70-73. DOI: 10.51559/ptji.v6i1.274 Alavian F. & Ghasemi S. CRISPR-Based Therapy for Ischemic Stroke: A Narrative Review. Cell Mol Neurobiol (2026). https://doi.org/10.1007/s10571-025-01662-x Yang Y, Zhu H, Xiong T, Li S. Inflammatory Biomarkers in Ischemic Stroke: Mechanisms, Clinical Applications, and Future Directions. Neurosurgical Subspecialties. 2025;1(4):188-196. doi: 10.14218/NSSS.2025.00029.
WEB SOURCE : https://research.columbia.edu/use-recombinant-dna-submission-approval-requirements https://chatgpt.com/ -> with open discussion and trusted source