SOT therapy for Lyme is experimental, expensive—and full of potential.

Part One of a two-part series.

By Maria Marian, ND, MSE

For many people facing chronic infections such as Lyme disease, Epstein–Barr virus (EBV), herpes simplex virus (HSV-1 and HSV-2), or cytomegalovirus (CMV), the journey can be long and frustrating.

Antibiotics, antivirals, herbal therapies, and IV treatments may help initially, yet symptoms often persist or recur. This has led both patients and clinicians to explore innovative therapies that move beyond conventional antimicrobial approaches.

One such emerging option is Supportive Oligonucleotide Therapy (SOT), also referred to as antisense oligonucleotide therapy. Although still considered experimental in the context of Lyme and chronic viral infections, SOT builds upon decades of genetic medicine research and has even reached FDA approval in select infectious and cancer-related applications.

What is SOT?

At its core, SOT is a gene-silencing technique. Scientists design a short synthetic strand of nucleic acid (called an oligonucleotide) that binds to a very specific piece of genetic code inside the pathogen—such as Borrelia burgdorferi (the bacterium that causes Lyme disease) or EBV.

When this oligonucleotide binds, it blocks the pathogen’s ability to produce a protein essential for replication or metabolism. In simple terms, it’s like removing a crucial page from the pathogen’s instruction manual. Without that instruction, the organism can’t replicate efficiently, and its numbers gradually decline.

This strategy falls under the larger field of “antisense therapy.” The term comes from the fact that these therapeutic molecules bind to the “sense” strand of RNA or DNA, neutralizing its ability to produce proteins.

Reference: Crooke ST. Antisense Drug Technology: Principles, Strategies, and Applications. CRC Press; 2008.

How the therapy works

The process of SOT treatment involves several carefully orchestrated steps:

1. Blood Draw & Testing – A blood sample is taken and analyzed using molecular techniques such as PCR to identify which pathogens are active.
2. Custom Design – A laboratory designs a patient-specific oligonucleotide tailored to silence a genetic target in that pathogen. Newer approaches like QRE-strain technology (Quasispecies Resistant Engineered strain) aim to account for genetic variations in pathogens, ensuring the oligonucleotide is effective across slightly different strains.
3. Infusion – Once prepared, the oligonucleotide solution is returned to the clinic and administered as a single intravenous infusion.
4. Ongoing Action – Unlike antibiotics or antivirals that are metabolized quickly, SOT molecules remain active for months (often up to six months), continuously working “day and night” to suppress pathogen replication.

The Science Behind It

Antisense oligonucleotides are not a new idea. In fact, the first FDA-approved antisense therapy, fomivirsen (Vitravene), was approved in 1998 to treat CMV retinitis in immunocompromised patients【PMID: 9815174】. Since then, several antisense and RNA-based drugs have reached the market for conditions ranging from high cholesterol (mipomersen) to spinal muscular atrophy (nusinersen)【PMID: 29191460】.

In infectious disease specifically:

• CMV: Fomivirsen demonstrated that gene-silencing therapy can effectively reduce viral activity in humans.
• Herpesviruses: Preclinical studies have shown that antisense molecules can block HSV and EBV replication in vitro【PMID: 19920191】.
• Lyme disease: Pilot clinical data suggest that one or two SOT infusions can lead to statistically significant reductions in Borrelia burgdorferi DNA levels detected by PCR. For viral infections, two or three treatments may be needed to achieve measurable decreases.

While more research is essential, these early findings provide a rationale for SOT as a potential adjunctive therapy in chronic infections where other approaches fall short.

Why patients are interested

For individuals struggling with persistent infections, SOT offers several appealing features:

• Precision targeting: Instead of broadly killing microbes (as antibiotics do), SOT goes after one critical genetic sequence, leaving other microbes untouched.
• Durability: A single infusion provides months of activity, reducing the need for daily medication.
• Immune-independent mechanism: Because SOT directly silences genes, it doesn’t rely on the immune system’s strength—a key advantage for patients with immune dysfunction.
• Potential synergy: Many clinicians use SOT alongside integrative therapies (nutrition, detoxification, antimicrobials) for a more comprehensive approach.

Current limitations

Despite the excitement, it’s important to emphasize what SOT is not at this stage:

• It is not FDA-approved for Lyme disease, EBV, or HSV. Its only infectious disease approval was for CMV retinitis, and that drug is no longer commercially available.
• Clinical research in Lyme and chronic viral infections is preliminary, mostly limited to small pilot studies and case reports.
• Costs can be significant, and insurance rarely covers it.
• The decline in pathogen burden is gradual, and multiple treatments may be required.

In short: SOT is promising, but it remains an emerging therapy.

Looking ahead with both hope and caution

The field of RNA medicine is growing rapidly, with antisense oligonucleotides, small interfering RNAs (siRNAs), and messenger RNA (mRNA) therapies transforming the landscape of medicine. With continued research, we may see gene-silencing strategies like SOT become mainstream tools in the fight against chronic infections.

For now, patients and clinicians should approach SOT with both hope and caution—hope that it represents a real step forward in treating persistent pathogens, and caution because large, peer-reviewed trials are still needed to fully establish safety, efficacy, and long-term outcomes.

Part two will be published next week.

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