Gene Editing for Rare Genetic Diseases: Is An Equitable Future Possible?

By Sai Chamarthi


“The pain I would feel in my body was like being struck by lightning and hit by a freight train all at once,” Victoria Gray remarks.¹ She recounts her experience living with sickle cell disease (SCD) in front of more than 500 leading scientists, policymakers, and enthusiasts at the Third International Summit on Human Genome Editing.

Gray was only three months old when she was diagnosed with SCD, a rare genetic blood disorder characterized by misshapen red blood cells and bouts of extreme pain.2 The defective cells either prematurely die, causing anemia, or obstruct the bloodstream, preventing oxygen circulation and resulting in painful episodes known as “crises”. Gray has primarily experienced the latter.3

Growing up, this meant that playtime was replaced by doctor visits, school with extended hospital stays, and meaningful life milestones with a blur of constant trauma. But Gray maintained hope and control where she could, getting married and raising four children, pursuing college to fulfill her dreams of becoming a nurse (though she eventually had to drop out due to health limitations), and celebrating life’s small wins.2  

For patients like Gray, treatment options were limited. She was constantly administered a slew of potent pain medications along with blood transfusions, but these reactive therapies expectedly didn’t resolve the underlying etiology, nor did they provide sufficient long-term symptomatic relief.4 Until recently, the only available cure–a bone marrow transplant–was solely available from eligible sibling donors. Narratives like this sadly reflect the lives of many with rare diseases.


A Beacon in the Shadows 

SCD is just one of approximately 10,000 known rare diseases, which are classified in the United States as conditions that affect fewer than 200,000 individuals.5 Together, they impact an estimated 25 to 30 million Americans (i.e. 10 percent of the population) and present individuals with a spectrum of functional limitations, oftentimes positioning them on the brink of death.6 The cumulative economic burden is no less significant, with US healthcare spending on these diseases totaling nearly $966 billion in 2019.7 Regardless, over 90 percent of rare diseases still lack viable interventions.7

Instead, the beacon of hope stems from the fact that almost 80 percent of rare diseases are genetically rooted.7 Recent advancements in genomic sequencing and gene editing have uniquely ushered in an era of precision medicine that can innovate diagnostics and therapeutics, respectively. By discovering the genetic underpinnings of a specific condition, gene editing technologies such as CRISPR/Cas9 systems can be employed to offer targeted interventions and improve clinical outcomes.

Gray’s story is recognized because she was the first SCD patient to be successfully treated with an experimental CRISPR-based therapy called Casgevy. Her red blood cells were extracted, genetically edited in vitro to produce more fetal hemoglobin, and reintroduced into her bloodstream following four days of chemotherapy.2 It’s particularly notable that she volunteered for the clinical trials despite the uncertainties linked with the novel therapeutic. For all she knew, CRISPR could have exacerbated her condition, but even the slight prospect of a painless future was enough to push her to enroll.

Since Gray’s success story in 2019, the clinical trials jointly conducted by CRISPR Therapeutics and Vertex Pharmaceuticals have published promising results in more than 75 other patients.8 In fact, the United Kingdom approved the commercial use of Casgevy in late 2023 for treating sickle-cell disease and beta thalassemia, making it the first CRISPR-based treatment on the market.9 Other clinical trials are in progress and are projected to follow suit. 

Yet with these technological advancements bringing us closer to what was thought to be only possible far in the future, an often forgotten implication lies in equitable access to care. When the disproportionate access to treatment improves the lives of some populations but leaves others to unjustly endure a treatable condition, existing health disparities are amplified along multiple facets. In fact, academics such as Anya Prince, Associate Professor of Law at the University of Iowa College of Law, argue that these novel therapeutics may lead to “dwindling social support and limited resources for patient populations with diseases that can be cured” as society adapts to newer modalities of care.10 Therefore, conversations must happen to ensure these communities aren’t neglected in implementation.


Inclusivity in Research and Distribution

The CDC defines health equity as “the state in which everyone has a fair and just opportunity to attain their highest level of health”.11 Inequities can then be extrapolated as the differentials in acquiring these opportunities. 

Namely, one necessary component is ensuring that the research backing CRISPR-related technologies represents its end users. Though millions of Americans collectively cope with rare genetic diseases, the number of people impacted by any one of these conditions is far fewer. As such, diseases with “smaller, more diffuse, or less empowered” patient populations are less prioritized than those with greater public attention and funding.7

On the one hand, the commercial viability of solutions to these under-prioritized genetic diseases is questionable, perhaps justifying this observation. For instance, an effective gene therapy called Strimvelis was developed to target a genetic disorder of the immune system, but was eventually pulled from the market due to net financial losses incurred by the distributing company.12 In these instances, the lack of a sufficient market rationalizes why research for rare diseases may be limited.

On the other hand, such an approach undermines the humanistic component of disease by painting each condition as merely an opportunity to profit. This should not be the standard if minority communities, who generally comprise these under-prioritized populations, are to access these treatments. In Strimvelis’ case, a European nonprofit company recently acquired the license to manufacture and market the therapy, highlighting a novel distribution channel that can potentially balance these tradeoffs.12 

Nonetheless, even for rare genetic diseases that are relatively more prevalent, inherently racist agendas exist and raise concerns of access and efficacy. For one, racial and ethnic minority populations are underrepresented in the genomic sequencing studies that prelude genetic discoveries. One study found that despite more than 76 percent of the world’s population residing in Asia or Africa, 72 percent of sequencing is conducted with participants from just three locations: the US, the UK, and Iceland.13 This incomplete understanding of diverse genetic architectures may impede the accurate detection of disease-causing mutations in underrepresented populations and their subsequent clinical translation into necessary gene editing solutions.

A clear example is the distinction between treatment options in the US for two rare genetic diseases: cystic fibrosis and sickle cell disease treatment. Though SCD is a more prevalent disease, there has only been one FDA-approved drug targeting it since 1996, while cystic fibrosis has had nine.14 Among these cystic fibrosis therapies, many are more effective in treating Euro-American patients than Hispanic patients, despite the latter experiencing higher mortality rates.7 Treatment centers for cystic fibrosis also receive greater funding and have more locations throughout the country.15 The most glaring difference is that cystic fibrosis predominantly impacts white populations, while SCD primarily affects African Americans.

In the case of the SCD-treating therapy Casgevy being the first commercially available CRISPR system, additional concerns are raised with African American patients like Gray being the pilot subjects for medical technologies with significant uncertainties in clinical outcomes. This falls in line with a history of demonstrated exploitation of minority communities in public health research and continued discrimination in treatment access following development (e.g. Tuskegee syphilis study, the case between Havasupai Tribe members and Arizona State University, etc.).15,16

In discovering gene editing solutions, society must pay careful attention to ensure we ethically incorporate marginalized groups back into research and development. When systems are designed to solely address the needs of higher socioeconomic classes who generally exercise greater voice, power, and education, an imbalance of care is created. On the one hand, people who possess enough resources can ameliorate their living conditions. On the other hand, people who are under-resourced will be forced into a lifetime of suffering, despite the possibility of a cure. Ultimately, the question becomes not whether we will create these gene editing therapeutics, but which ones will be prioritized, and who will benefit from these decisions?


Fundamental Cause Theory

In the context of medical technologies, there is a perspective known as fundamental cause theory. It postulates that socioeconomically advantaged communities disproportionately benefit from innovations when compared to disadvantaged communities, causing health inequities to linger in society.15 This can result from previously raised concerns of inclusivity, but it can also be a consequence of the greater educational and financial resources available to the advantaged populations. Such assets enable them to become early adopters of these technologies and proactively access treatment options without significant hurdles.


Financial Barriers

Cost is one of the critical barriers to care. For instance, Casgevy’s commercialization has recently prompted discussions of its market value. Since it potentially offers a one-time cure for SCD, which has a $4-6 million lifetime treatment cost, Casgevy is projected to exceed the price of non-CRISPR gene therapies, raising the concern of health justice.15 In Gray’s case, she was able to access Casgevy due to research funding backing the clinical trials, but this may not have been possible for her outside the context of drug development. 

In response, insurance companies have been searching for methods to cover these treatments, but this may not entirely be feasible with current healthcare infrastructure. According to one study, if an SCD therapy like Casgevy were to cost $1 million per patient, it would “cost Medicaid $55 billion or roughly 85 percent of Medicaid’s total spending on outpatient drugs in 2017”.17 Even if larger insurance companies and state Medicaid programs developed a way to manage this burden, underserved medical populations, who are either commonly covered by smaller insurance companies or are uninsured, may still be sidelined. This calls for innovative pricing and payment plans to parallel the advances in medical technology innovations.

Additionally, the standard of care is dynamic, and healthcare norms are constantly evolving to accommodate societal changes. For instance, cardiac pacemakers have become a steady option of care for cardiac maladies nowadays despite their cost, so it is possible that gene editing solutions will follow suit.18 Regardless, this demonstrates an example of longer-term stabilization, and economic disparities must still be accounted for in early implementation stages.


Geographic Barriers

Rare genetic diseases also oftentimes go undiagnosed or misdiagnosed for long periods of time, which, in turn, delays the correct treatment. This is even more common in hospitals in low-income neighborhoods where personnel are less likely to have the specialized disease expertise to accurately diagnose, meaning drugs and treatments may be inaccurately prescribed to patients.6

Even in instances where a diagnosis is possible, newer treatments follow a trickle-down schema, meaning healthcare centers in wealthier areas will gain access to them before those in poorer areas.19 This can be partially attributed to the differences between the workforces in these locations. For treatments such as gene editing, proper infrastructure and special training are required for the procedures.20 Therefore, patients from locations where gene editing is introduced later may find themselves spending more money on traveling to other locations or simply being left untreated during the initial stages of the technology rollout.

Another aspect that’s commonly ignored is the environmental contributions to disease manifestation, which are heavily shaped by one’s place of residence. A prime example lies with those who may be genetically predisposed to skin cancer.13 Their risk of contracting the disease is significantly greater if they live in areas with greater sunlight exposure, so it is difficult to conceive of how a technology as precise as CRISPR could tackle such a variable phenomenon. 

For point mutations like those that cause SCD, the etiology is heavily based on genetics, contributing to its early success.15 But for others where the environment plays a bigger role, the answer may lie in greater representation of genomic sequencing to more comprehensively identify positions of mutations. Not only does this mean more representation in terms of racial and ethnic minority groups, but also geographically with rural and low-income communities, and with regard to various age groups.


Final Thoughts

In the end, if healthcare is not representative of or is withheld from these communities, existing disparities will further generate what Jennifer Doudna, one of the co-founders of CRISPR, calls the “gene gap,” where only certain groups can access this “boutique technology”.21 Therefore, as meaningful narratives like Gray’s are considered, this is a gentle reminder that though dismantling systemic health inequities may be a Herculean task, micro-level avenues for advocacy exist to work towards ensuring medical innovations don’t leave anyone behind.



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