How CRISPR Helps with Genetic Disorders
300 million people worldwide live with rare diseases—most of them genetic. For decades, families have faced an impossible reality: a diagnosis with no treatment, years spent searching for answers, and watching their loved ones' conditions progress while science struggles to catch up. The gene therapy field has brought new hope, particularly through CRISPR technology. But the full picture is more nuanced than headlines suggest.
The Problem: Families Left Behind by Medical Progress
95% of Rare Diseases Have No Treatment
While medicine has made remarkable strides in treating common conditions, rare genetic disorders remain largely unaddressed. According to the Lancet Global Health, approximately 95% of rare diseases lack FDA-approved treatments. This affects more than 30 million Americans and hundreds of millions globally.
The numbers reveal the scale of unmet need:
Over 10,000 rare diseases have been identified
30% of children with rare diseases die before age 5
The Diagnostic Odyssey Takes Years
Before families can even consider treatment options, they must first obtain an accurate diagnosis—a process that averages 4.8 years. During this period, patients undergo an average of 17 clinical encounters, bouncing between specialists who may not recognize rare disease symptoms.
This delay has consequences beyond frustration. Many genetic conditions are progressive, meaning irreversible damage accumulates during the years spent seeking answers. By the time a diagnosis arrives, critical treatment windows may have closed.
The Financial and Emotional Toll on Families
The economic burden of rare diseases in the United States reached $997 billion in 2019, with an average cost of $266,000 per patient annually—roughly 10 times the cost of managing common diseases. This includes:
$449 billion in direct medical costs
$437 billion in productivity losses
$73 billion in non-medical expenses
$38 billion in out-of-pocket healthcare costs
Beyond financial strain, the psychological impact is severe. Studies show that 89.6% of caregivers experience clinical distress levels, with over half reporting that healthcare providers never asked about their mental health during the diagnostic journey.
CRISPR Offers Hope for Genetic Correction
How CRISPR Gene Editing Works
CRISPR-Cas9 functions as a precise molecular tool that can locate and modify specific DNA sequences. The system consists of two components: the Cas9 enzyme, which acts as molecular scissors to cut DNA, and a guide RNA that directs Cas9 to the exact location in the genome requiring modification.
Once the guide RNA finds its target sequence, Cas9 creates a double-strand break in the DNA. The cell's natural repair machinery then fixes this break, either by joining the ends back together (which can disable a faulty gene) or by using a provided template to insert corrected genetic information.
First FDA-Approved CRISPR Therapy
On December 8, 2023, the FDA made history by approving Casgevy, the first CRISPR-based therapy. This treatment targets sickle cell disease and beta-thalassemia, two blood disorders affecting tens of thousands of Americans.
Clinical trial results showed remarkable efficacy:
93.5% of sickle cell patients (29 of 31) achieved freedom from severe pain crises for at least 12 consecutive months
91.4% of beta-thalassemia patients (32 of 35) became transfusion-independent
By Q3 2024, approximately 40 patients had entered the Casgevy treatment process, marking the transition from experimental therapy to real-world application.
Expanding Clinical Applications
The gene editing field has grown rapidly. As of February 2025, approximately 250 clinical trials involving gene-editing therapeutic candidates are underway, with more than 150 currently active. These trials target conditions ranging from inherited blindness to cardiovascular disease to various cancers.
Beyond traditional CRISPR-Cas9, newer approaches have emerged:
Base Editing: This technique converts single DNA letters without creating double-strand breaks, potentially reducing certain safety risks. Beam Therapeutics dosed their first patient in January 2024 for a base editing therapy targeting sickle cell disease.
Prime Editing: Described as a "search-and-replace" system, prime editing can perform all types of base substitutions plus small insertions and deletions. While still in preclinical development, it has the potential to address roughly 89% of known disease-causing genetic variants.
Real Results in Rare Disease Treatment
Recent clinical data demonstrates CRISPR's potential across multiple conditions:
Hereditary Blindness: In trials of EDIT-101 for Leber congenital amaurosis type 10, 79% of patients showed vision improvement, with 21% experiencing clinically meaningful gains.
Hereditary Angioedema: NTLA-2002 trials showed 60-95% reduction in plasma kallikrein levels, with most patients remaining attack-free for over 18 months.
Cardiovascular Disease: VERVE-102 trials demonstrated an average 59% reduction in LDL cholesterol at the highest dose, with no serious adverse events.
The Reality: CRISPR Has Limitations
Timeline and Accessibility Challenges
While CRISPR represents a major advance, the path from diagnosis to treatment remains long. The full Casgevy treatment process takes 9-12 months and includes:
2-3 months for evaluation and eligibility determination
1-2 months for stem cell collection
3-6 months for laboratory processing and CRISPR editing
4-6 weeks of intensive inpatient care for conditioning and infusion
Months of recovery and monitoring
Currently, Casgevy is available at only 35+ authorized treatment centers across the United States, primarily at major academic medical centers. This geographic limitation means many families must relocate temporarily or travel extensively for treatment.
Cost Barriers
At $2.2 million per patient, Casgevy's price tag reflects the extensive development costs and manufacturing challenges of personalized gene therapies. While cost-effectiveness analyses suggest this may be reasonable compared to lifetime disease management costs, the upfront financial burden creates access challenges.
Insurance coverage is evolving. For 2025, Medicare established maximum add-on payments of $1.65 million for Casgevy. A new federal-state partnership launched in January 2025 aims to improve Medicaid access through negotiated discounts and outcomes-based pricing.
Safety Considerations and Unknowns
CRISPR therapies require myeloablative conditioning—high-dose chemotherapy that destroys existing bone marrow to make room for edited cells. This conditioning causes significant side effects including:
Severe immunosuppression
Risk of infection
Potential fertility impacts
Weeks of hospitalization
Additionally, research shows that over 80% of people have pre-existing antibodies against Cas9 proteins, which could trigger immune responses or reduce treatment efficacy. Long-term safety data remains limited, with the FDA requiring 15-year follow-up for Casgevy patients.
Not All Genetic Disorders Are Suitable for CRISPR
CRISPR works best for specific types of genetic mutations—particularly those requiring permanent correction or gene insertion. However, many genetic disorders involve:
Toxic gain-of-function mutations where reducing protein levels (not correcting them) is beneficial
Splicing defects that affect how genes are read, which cannot be addressed by genome editing
Conditions requiring reversible intervention where permanent DNA changes pose unacceptable risks
Situations where the therapeutic window has passed and damage is already irreversible
Antisense Oligonucleotides: A Complementary Approach
How ASO Therapy Works Differently
Antisense oligonucleotides (ASOs) take a fundamentally different approach from CRISPR. Rather than permanently editing DNA, ASOs are short synthetic molecules that bind to RNA—the messenger between DNA and protein production. This allows ASOs to:
Reduce levels of toxic proteins by triggering RNA degradation
Modify how genes are read by changing splicing patterns
Increase beneficial protein production by blocking inhibitory signals
Critically, ASO therapy does not alter the genome itself. The effects are reversible, and treatment can be stopped if adverse effects occur.
Proven Track Record in Rare Disease
The FDA has approved 14 ASO therapies, with several showing remarkable long-term success:
Spinraza (nusinersen) for spinal muscular atrophy:
Approved in December 2016
Real-world data shows 96% of patients achieved improvement or stability
Over 14,000 patients treated worldwide with 10+ years of safety data
Qalsody (tofersen) for SOD1-ALS:
Approved in April 2023
Targets toxic protein accumulation through RNA degradation
Demonstrates reversible approach for gain-of-function mutations
Recent 2024 Approval: TRYNGOLZA (olezarsen) received FDA approval on December 19, 2024, for familial chylomicronemia syndrome, showing 77-81% reduction in target protein levels.
When ASO Therapy Excels
ASO approaches work particularly well for conditions where CRISPR faces limitations:
Toxic Gain-of-Function Disorders: Diseases caused by harmful protein accumulation, such as Huntington's disease and certain forms of ALS, benefit from ASO's ability to reduce protein levels without permanent genome changes.
Splice-Correction Diseases: Approximately 15% of genetic diseases result from splicing defects—errors in how genetic information is processed into proteins. ASOs can redirect splicing patterns with single-nucleotide precision, addressing problems that genome editing cannot fix.
Progressive Neurological Conditions: For diseases affecting the brain and nervous system, ASO delivery through intrathecal injection provides direct access to the central nervous system. Many degenerative conditions benefit from reversible intervention that can be adjusted as the disease evolves.
Adult-Onset Conditions: Pre-existing immunity to viral vectors often prevents CRISPR delivery in adults. ASO therapies don't face this barrier.
Nome's Approach: Personalized ASO Therapy at Scale
The N-of-1 Medicine Framework
Traditional drug development assumes one therapy will work for many patients. But for ultra-rare genetic conditions—those affecting dozens or even single individuals—this model breaks down. N-of-1 medicine flips the paradigm: custom-designing therapy for individual patients based on their unique genetic mutations.
In 2019, researchers at Boston Children's Hospital created the first N-of-1 ASO therapy for a child named Mila, who had a unique form of Batten disease. The timeline was remarkable: from genetic diagnosis to first dose in under one year. The treatment reduced her seizures from 30 per day to fewer than 10, demonstrating proof-of-concept for personalized ASO therapy.
FDA Guidance Enables Faster Development
In 2021, the FDA released comprehensive guidance specifically for individualized ASO therapies, establishing a streamlined regulatory pathway. This guidance allows:
Abbreviated safety testing leveraging data from approved ASOs with similar chemical structures
Simplified manufacturing requirements for small batches
Accelerated review timelines for life-threatening conditions
Use of computational analysis to predict off-target effects
This regulatory framework recognizes that ASOs share a well-characterized chemical backbone. When designing a new ASO for a different genetic target, developers can reference decades of safety data from the 14+ approved ASO drugs, dramatically reducing development time and cost.
Speed and Cost Advantages
Nome's approach leverages these regulatory pathways combined with AI-enabled design platforms to compress traditional development timelines:
Traditional gene therapy development: 5-10+ years, $500 million to $1 billion N-of-1 ASO development: 6-12 months, average cost $1.6 million
This speed matters critically for progressive diseases. Every month of delay allows irreversible damage to accumulate. For neurodegenerative conditions where neurons cannot regenerate after death, early intervention during the diagnostic odyssey could mean preserving function versus permanent disability.
The 30-Day Therapeutic Plan
Nome's process begins with intake and eligibility assessment, where genetic data is analyzed to determine if a custom ASO is appropriate for the specific mutation. Within approximately 30 days, Nome assembles a development-ready plan covering:
ASO molecule design optimized for the target sequence
Safety and toxicology requirements
Chemistry, manufacturing, and controls (CMC) strategy
Regulatory pathway and program economics
This rapid planning phase leverages AI-enabled design tools that can predict ASO efficacy and minimize off-target effects before synthesis. Rather than conducting extensive trial-and-error screening, computational models identify optimal sequences, reducing both time and cost.
Partner Orchestration Removes Family Burden
Developing a custom therapy requires coordination across multiple specialized vendors: manufacturing facilities, testing laboratories, regulatory consultants, and clinical delivery teams. Nome manages this orchestration, connecting families with world-class partners appropriate for their specific treatment.
This removes a significant burden from families already managing complex medical care. Rather than navigating an unfamiliar landscape of pharmaceutical development, families work with Nome's team to move from triage to action while maintaining decision-making control.
Transparent, Milestone-Based Pricing
Following the free intake and 30-day plan, ongoing development operates on a transparent monthly fee structure with milestone-based pricing. This model differs from traditional pharmaceutical development, where costs remain opaque until late-stage failure or success.
For families, this transparency enables informed decision-making about whether to pursue treatment development. It also aligns incentives—Nome succeeds when families achieve their therapeutic goals.
Two Approaches, One Goal: Treating the 95%
CRISPR and ASO Therapies Are Complementary
The gene therapy landscape benefits from multiple technological approaches because different genetic disorders require different solutions:
CRISPR excels when:
Permanent genetic correction is advantageous
Loss-of-function mutations require gene insertion
One-time treatment is preferable to ongoing dosing
The condition affects blood cells accessible through ex vivo editing
ASO therapy excels when:
Reversible modulation provides safety advantages
Toxic gain-of-function requires protein reduction
Splicing defects cannot be addressed by genome editing
Rapid development is critical for progressive disease
CNS delivery is required
Both approaches expand treatment options for the 95% of rare diseases lacking therapies. The field needs continued advancement in CRISPR, ASO, gene replacement, and other modalities to address the full spectrum of genetic disorders.
The Real Barrier Is Time
For families facing progressive genetic conditions, the primary enemy is time. The average 4.8-year diagnostic odyssey already consumes critical treatment windows. Adding years of drug development on top of diagnostic delays means many patients never receive intervention early enough to make a difference.
ASO therapy's development speed—measured in months rather than years—offers hope for families who cannot wait. When neurons are degenerating, organs are failing, or development is delayed, every week matters. The ability to design, test, and deliver a custom therapy within 12 months changes what's possible.
Looking Forward: Accessible Personalized Medicine
The approval of Casgevy marks the beginning of the CRISPR therapy era, with 10-20 gene editing approvals expected annually by 2025. Simultaneously, the N-of-1 ASO framework is maturing, with 25 case dossiers submitted to N=1 Collaborative in 2024 and international programs launching in the UK, Netherlands, and Japan.
The future of rare disease treatment isn't CRISPR versus ASO—it's CRISPR and ASO working together to address different aspects of the 95% problem. For families, this means more options, faster access, and realistic hope that a diagnosis doesn't have to mean a dead end.
Nome's mission centers on making personalized ASO therapy accessible for rare genetic conditions where speed, reversibility, and precise targeting matter most. By combining AI-enabled design, streamlined regulatory pathways, and expert partner coordination, Nome aims to transform rare disease treatment from a multi-year, multi-million dollar endeavor into a months-long journey toward meaningful intervention.
For the 300 million people worldwide living with rare diseases, progress cannot come fast enough. Every technological advance—whether CRISPR, ASO, or future innovations—brings us closer to a world where "rare" no longer means "untreatable."
