Madison Area Lyme Support Group

This is Part Two of a series on Supportive Oligonucleotide Therapy (SOT),  a form of antisense oligonucleotide therapy. SOT is a personalized, gene-silencing treatment designed to disrupt pathogens like Lyme disease. Read Part One here.

10/8/25

By Maria Marian, ND, MSE

The idea of silencing genes to weaken pathogens may sound futuristic, but antisense oligonucleotide therapies have already proven themselves in medicine.

Cancer research: Multiple antisense drugs have been studied in oncology to block genes that promote tumor growth and survival (e.g., Bcl-2, EGFR). While not all succeeded in trials, these studies helped refine delivery methods and safety monitoring【PMID: 19164450】.

FDA approval for infection: In 1998, fomivirsen (Vitravene) became the first antisense drug approved for human use, targeting CMV retinitis in immunocompromised patients【PMID: 9815174】. This milestone showed that gene silencing could work safely against viruses in humans.

Emerging infectious disease applications:

• Laboratory studies demonstrate antisense oligonucleotides can inhibit replication of HSV, EBV, hepatitis viruses, and influenza【PMID: 19920191】.
• In Lyme disease, small clinical series using SOT have reported significant reductions in Borrelia burgdorferi DNA copy numbers in blood following one or two infusions, as measured by PCR. Viral infections like EBV and HSV may require more sessions to achieve measurable results.

Although the published data are limited, these results are encouraging for patients who have exhausted conventional treatment options.

The Patient Experience

From a patient’s perspective, SOT is different from antibiotics, antivirals, or even most integrative therapies.

• One infusion, long effect: Instead of daily or weekly medication, SOT is given as a single intravenous infusion, yet its activity can last up to six months.
• Gradual improvement: Because the therapy slowly reduces pathogen replication rather than rapidly killing organisms, many patients notice changes gradually over weeks to months.
• Reported benefits: Improvements may include reduced fatigue, better cognitive clarity, less pain, and fewer flares of viral reactivation.
• Side effects: Most reported side effects are mild—such as temporary fatigue, flu-like symptoms, or localized reactions during infusion. Serious side effects appear rare in current reports.

That said, responses vary. Some patients may need multiple SOT cycles for sustained benefit, and others may not notice dramatic changes. As with all therapies, individual outcomes depend on many factors, including immune status, co-infections, and overall health.

Benefits and Strengths of SOT

Patients and clinicians exploring SOT often highlight its unique advantages:

• Precision: Targets one critical sequence of the pathogen’s genome with minimal off-target effects.
• Immune-system independent: Works even when immunity is suppressed or exhausted.
• Continuous action: Active day and night for months, unlike short-lived antibiotics or antivirals.
• Compatibility: Can be combined with integrative approaches (herbal protocols, detoxification, nutritional support) for a systems-based strategy.

Limitations and Open Questions

Despite its promise, SOT is not a silver bullet. Important limitations remain:

• Limited clinical research: Most studies so far are pilot projects or case series, not large randomized controlled trials.
• Not FDA-approved for Lyme or herpes viruses: Currently, its approved infectious disease application (fomivirsen for CMV) is historical. Use for Lyme, EBV, or HSV is off-label/experimental.
• Cost: Treatments are highly individualized and can be expensive, often not covered by insurance.
• Unknowns in long-term outcomes: While short-term safety looks good, more research is needed to assess durability of remission and long-term effects.

For these reasons, patients considering SOT should do so under the guidance of a clinician familiar with both its potential and its uncertainties.

Where Does SOT Fit in Chronic Lyme Care?

SOT should be thought of as a potential adjunctive therapy—not a replacement for all other treatments. In chronic Lyme and co-infections, successful treatment usually requires a layered approach, addressing:

• Microbial burden (Borrelia, Bartonella, Babesia, viruses, parasites)
• Immune regulation
• Detoxification and environmental exposures (mold, metals, chemicals)
• Mitochondrial and hormonal health
• Lifestyle and resilience factors

Within that framework, SOT may serve as a targeted tool to reduce microbial load when conventional antimicrobials or integrative protocols have plateaued.

The Future of Gene-Silencing Therapies

The broader field of RNA-based medicine is expanding at remarkable speed. In recent years, the FDA has approved multiple oligonucleotide drugs for rare genetic diseases, including:

• Nusinersen (Spinraza): spinal muscular atrophy【PMID: 29191460】
• Eteplirsen: Duchenne muscular dystrophy
• Patisiran: hereditary transthyretin amyloidosis

These approvals show that oligonucleotide therapies can be safe, effective, and commercially viable. As technology advances, it is likely we will see more robust clinical trials for antisense therapies in infectious diseases, improved delivery systems that increase effectiveness and reduce costs, and expanded targets, not only for microbes but also for the inflammatory pathways they trigger.

For the Lyme community, this represents a hopeful horizon: a class of therapies designed with molecular precision to address infections that often resist conventional treatment.

Final Thoughts

Supportive Oligonucleotide Therapy is an exciting example of how genetic medicine is moving from the laboratory into clinical care. While not a cure-all, and not yet backed by large-scale Lyme disease trials, it offers a promising option for patients whose infections have proven stubborn to standard therapies.

As with all emerging treatments, the best approach is a balance of hope and caution: hope that this new tool may bring relief, and caution in recognizing the need for further research and informed decision-making.

For patients and families dealing with the daily challenges of chronic Lyme and viral co-infections, SOT reflects a broader truth in medicine today—sometimes the way forward is not more of the same, but something entirely new.

Click here for Part 1:  SOT therapy for Lyme is experimental, expensive—and full of potential

Maria Marian, ND, MSE, is a naturopathic physician at Jyzen Wellness in Mill Valley, California. In addition to her Doctorate of Naturopathic Medicine, she holds both a Bachelor and Master of Science in Chemical Engineering. She specializes in complex chronic illness, Lyme disease, and integrative approaches to immune dysfunction. Follow her on Instagram: @dr.marian.nd

References

1. Perry CM, Balfour JA. Fomivirsen. Drugs. 1999;57(3):375–380. PMID: 10080450.
2. Crooke ST. Antisense Drug Technology: Principles, Strategies, and Applications. CRC Press; 2008.
3. Stein CA, Castanotto D. FDA-Approved Oligonucleotide Therapies in 2017. Mol Ther. 2017;25(5):1069–1075. PMID: 28457632.
4. Kole R, Krainer AR, Altman S. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nat Rev Drug Discov. 2012;11(2):125–140. PMID: 22262067.
5. Khorkova O, Wahlestedt C. Oligonucleotide therapies for CNS disorders. Neurotherapeutics. 2017;14(4):827–840. PMID: 29191460.
6. Stein CA, Hansen JB, Lai J, et al. Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides. Nucleic Acids Res. 2010;38(1):e3. PMID: 19850725.