SOT Treatment for Lyme Disease

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SOT for Lyme Image from Marty Ross MD

Supportive Oligonucleotide Therapy (SOT) Background

Supportive Oligonucelotide Therapy (SOT) is a new treatment for Lyme disease. SOT is also called Antisense Oligonucelotide Therapy (ASOT) which is the term used in medical research papers. SOT uses laboratory derived nucleic acids (genetic code) that blocks production of disease causing proteins or even gene expression. These pieces of genetic code are called oligonucleotides. You can think of oligonucleotides as a genetic message.

For example, in Duchenne Muscular Dystrophy (DMD), SOT provides oligonucleotides that direct the correct production of a protein called dystrophin. People with muscular dystrophy are born with DNA that provides the wrong genetic message for dystrophin. SOT correction to the DNA message leads to production of dystrophin. This prevents the muscle damage seen in DMD.

In Lyme disease, a currently available type of SOT produced by RGCC in Greece uses oligonucleotides intended to stop germ growth and replication. Unlike the SOT therapy for Duchenne muscular dystrophy, the Lyme SOT is not a US Food and Drug Administration (FDA) approved drug. To be approved by the FDA, a therapy must have scientific evidence of safety and effectiveness. 

As I explain below, SOT does not alter DNA. It provides a short-term change to how the DNA blueprint is expressed.

There are currently nine SOT drugs approved by the FDA or European regulators to treat

  • Batten disease,
  • cytomegalovirus retinitis,
  • Duchenne muscular dystrophy,
  • familial chylomicronemia syndrome,
  • familial hypercholesterolemia,
  • hereditary transthyretin-mediated amyloidosis, and
  • spinal muscular atrophy.

According to Wikipedia there are nearly 50 SOT drugs in various levels of clinical trials. In my research, I am not able to identify one laboratory or human trial using SOT for Lyme disease.

Lyme Disease SOT Claims

In Lyme disease these oligonucleotides are being used to interrupt and block protein production required for the germ to replicate and grow. In theory, this leads to the death of existing germs and stops the spread of new germs. The clinics currently offering SOT therapy in the United States are purchasing non-FDA approved SOT drugs from a Greek genetic laboratory called RGCC. I have written RGCC to provide information about how their SOT actually works and to provide any scientific evidence of this. I have not received a response, so I cannot validate any claims made by these US clinics about the method of action or the benefit of the RGCC SOT product.

More About How SOT Works: A Genetic Primer

DNA, RNA, Oligonucleotides

Our genetic code that provides the blueprint for the production of proteins in the body is called DNA. The building blocks of DNA are called nucleic acids. There are five different kinds of nucleic acid: adenine, cytosine, guanine, thymine, and uracil. Thymine occurs only in DNA and uracil only in RNA. DNA is made of two strands of nucleic acids wound around each other.

The DNA message and directions for protein production are turned into RNA. RNA is a single strand of nucleic acids. DNA is found in the center of a cell. Once the RNA is made from the DNA, it moves to part of the cell where protein is made. The RNA’s directions are read in a protein production factory in the cell called a ribosome. If the RNA is readable, a specific protein coded by the RNA is made.

Oligonucleotides are short strands of nucleic acids. These strands are much shorter than RNA and DNA. Oligonucleotides are usually made of 15 to 20 nucleic acids.

How SOT Works

There are a variety of ways that SOT could work in Lyme disease. Below I discuss three of these ways. 

One way that SOT works is to provide oligonucleotides that bind to part of the RNA. This prevents the RNA from being read. These are blocking oligonucleotides that bind to a type of RNA called messenger RNA or mRNA for short.

Another way some SOT works is to bind to the mRNA and then cut it up into unreadable pieces.

There is also a type of microRNA called miRNA. This type of RNA regulates protein production or even germ replication. One type of SOT can bind the miRNA so it cannot work.

The RNA-SOT complex is eventually broken down in the cell by enzymes and replaced by new RNA. To be clear, SOT oligonucleotides do not change the DNA blueprint for the body or the DNA of germs.

Potential Problems with SOT

Reaching the Inner Cell

Our bodies make enzymes that break down RNA and oligonucleotides. This presents a problem, because the oligonucelotide could be destroyed before they even bind to RNA. The pharmaceutical industry has developed various modifications to the sugar backbone of the oligonucleotides to make them resistant to the breakdown enzymes.

SOT oligonucleotides have to cross the cell membrane, moving from outside to inside the cell, where they bind to RNA. This presents another problem for SOT. There are different ways the pharmaceutical companies are addressing this problem. For instance, some SOT is wrapped in microscopic layers of fat to increase absorption into the cells.

Safety Issues

There are potential safety issues. Some SOT therapies investigated by the pharmaceutical industry are shown to accumulate in organs like the kidney, liver, and spleen causing injury and toxicity.

Reaching Every Germ and Every Germ Type

SOT for Lyme needs to target each type of infection that is part of the person’s Lyme disease. This presents two problems. First, an SOT therapy should target Lyme germs and other infections if present like Bartonella and Babesia. Second, regarding Lyme, the germ hides away

  • inside cells,
  • in tissues with poor blood flow like tendons and scar tissue, and
  • deep within biofilm communities.

So it is very doubtful one infusion of SOT will reach all germs where they hide.

Lyme and Bartonella germs can exist in non-growing persister forms. SOT is designed to block growth and replication. By definition, persisters are not growing - they are hibernating. So it is very unlikely SOT could kill persister forms. For more information about Lyme persisters and persister treatments see How to Treat Persister Lyme. What Works?

RGCC, SOT Clinics, and Regulation

I suspect the FDA will eventually shut down centers providing Lyme SOT that is not FDA approved. My interpretation of FDA regulation suggests SOT oligonucleotides qualify as a drug. Drugs are subject to FDA regulation - the FDA only allows for the sale and use of approved drugs. Lyme SOT provided by RGCC is not an FDA approved drug. For more information read the FDA guidance.

Does Lyme Disease SOT Work?

I am not sure if current SOT for Lyme disease or coinfections works. As I discuss above, there are a number of obstacles for effective Lyme SOT. Given the barriers of SOT reaching every Lyme germ and likely not having activity against persister Lyme, I am doubtful this is an effective therapy for most people. 

I have seen a small number of patients in my clinic who have tried this therapy before seeing me with minimal to no effect. Some of my physician colleagues who offer this therapy claim some patients have improvement. Keep in mind that the average drug in clinical trials has a placebo effect of 35 percent. So if some claim benefit from SOT, it may have nothing to do with the oligonucleotides of SOT. I am interested in the experience of those that have received SOT. If you had SOT or know someone who did, please share with me whether it helped or not: [email protected]

Many therapies physicians offer in Lyme disease have limited science or studies showing they work. So the fact that Lyme SOT does not currently have any studies supporting its use, does not stop me from considering its use. However, even though many Lyme therapies have limited science, collectively health care providers share knowledge based on our experiences about whether or not a therapy works. So when research is lacking, we can learn what may work for Lyme based on our collective shared experiences. For SOT, there currently is not enough collective experience among patients, physicians, or other health care providers showing if SOT is effective. 

The Future of SOT

SOT therapies hold great promise for a variety of illnesses. It is possible a pharmaceutical company will find a way to address each of the concerns about safety and delivery I raise above. If it is developed correctly, Lyme SOT could change the face of Lyme disease treatment and improve patient outcomes. I look forward to seeing research in this area as it evolves.

My Questions to RGCC

Given all of the issues I raise above, I sent the following email to RGCC. I am still waiting for a response. This includes the type of questions each person considering Lyme disease SOT should ask.

I am an integrative medicine physician who treats chronic Lyme disease in Seattle. Washington USA. You can find more information about me and my practice at

I am interested in information about your approach to ASOT for Lyme disease. I have some questions for you.

1. What method are you using to stabilize the oligonucleotides to prevent degradation? I am aware of various oligonucleotide modifications that are currently employed:

  • Phosphorothioate
  • Phosphorodiamidate Morpholino Oligomer
  • Peptide Nucleic Acids
  • Locked Nucleic Acids
  • Nucleobase Modification

2. What method are you using to ensure uptake of the oligonucleotides into the various germs I treat in Lyme disease like borrelia, bartonella, babesia etc. Do you have any studies showing that your uptake methodology works?

3. What is your target mRNA for each of the various germs? Which mRNA are you trying to block, what does this mRNA control?

4. Why do you need the patient's blood, if you already know the target mRNA for each germ?

5. What is the cost of the oligonucleotides for one treatment? Does this increase if there is more than one infection targeted?

6. How do you know which germs to target? Do I indicate which germs I want ASOT when I send you the sample?

7. Do you have any safety studies for your ASOTs?

8. How are you avoiding the United States Food and Drug Administration labeling this as a Drug subject to their regulations and oversight?

I look forward to your response.


Marty Ross MD


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View Citations

  1. Dhuri K, Bechtold C, Quijano E, et al. Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development. J Clin Med. 2020;9(6):2004. Published 2020 Jun 26. doi:10.3390/jcm9062004
  2. FDA Guidance on Drug Classification:
  3. Wikipedia contributors. Antisense therapy. Wikipedia, The Free Encyclopedia. August 1, 2020, 14:27 UTC. Available at: Accessed August 1, 2020
  4. Enck P, Klosterhalfen S, Weimer K, Horing B, Zipfel S. The placebo response in clinical trials: more questions than answers. Philos Trans R Soc Lond B Biol Sci. 2011;366(1572):1889-1895. doi:10.1098/rstb.2010.0384

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About the Author

Marty Ross, MD is a passionate Lyme disease educator and clinical expert. He helps Lyme sufferers and their physicians see what really works based on his review of the science and extensive real-world experience. Dr. Ross is licensed to practice medicine in Washington State (License: MD00033296) where he has treated thousands of Lyme disease patients in his Seattle practice. 

Marty Ross, MD is a graduate of Indiana University School of Medicine and Georgetown University Family Medicine Residency. He is a member of the International Lyme and Associated Disease Society (ILADS) and The Institute for Functional Medicine.

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