Decoding Misconceptions Between RNA and Gene Therapy

Gene therapy. Genetic therapy. Gene editing. Gene writing. Gene silencing. DNA-based therapy. Nucleic acid-based therapy. RNA-based therapy. RNA editing. RNA writing. AON. ASO. siRNA. miRNA. RNAi… The list of terms used to describe RNA and gene therapies goes on.

Suzie Flowers, Principal Medical Writer at ApotheCom, explores the key differences between RNA and gene therapies and why clear terminology is crucial. With thousands of these therapies in development, confusion persists as terms like gene editing and RNA therapy are often misused. This leads to misunderstandings among healthcare professionals and patients alike. 

Given the rapid progress of RNA and gene therapies in recent years from scientific theory to clinical practice, it is perhaps unsurprising that the medical community has not yet developed a clear and agreed language to describe and differentiate between different types of advanced therapies. Instead, a whole host of new terms have emerged, driven by novel scientific discovery and by the desire of biopharmaceutical companies to differentiate their therapies from others with the development of new lexicons. Many of these terms are poorly defined (or understood) and inconsistently used, leading to ambiguity in an area of complex science.

The National Institutes of Health defines gene therapy as “a technique that uses a gene(s) to treat, prevent or cure a disease or medical disorder”, often by adding a functional gene copy or replacing a defective gene with a healthy version. Gene editing, which involves making targeted changes to DNA, such as the correction of a mutation, is generally considered to be a form of gene therapy. By contrast, RNA therapy refers to the prevention or treatment of disease using RNA-based molecules. Examples of RNA therapy include RNA-based antisense oligonucleotides (ASOs or AONs), which bind to messenger RNA (mRNA) via complementary base pairing and affect how it is processed, short interfering RNAs (siRNAs) and micro RNAs (miRNAs) – both forms of RNA interference (RNAi) that lead to the degradation of mRNA, and mRNA vaccines.

However, not all terms can be clearly defined. For example, genetic therapy is a term used by some as a synonym for gene therapy and used by others as a term to encapsulate both gene therapy and RNA therapy. And it is this lack of clarity that gives rise to misunderstanding, which in turn can lead to the spread of misinformation.

Medical communications agencies strive to bring clarity to semantics in situations like these, but it can sometimes feel like swimming upstream. As an example, one company recently brought to our attention an independent review paper that incorrectly listed their phase 3 siRNA therapy as a “gene therapy”. Another company found that when submitting a congress abstract about their RNA ASO therapy (which alters splicing of mutant mRNA to produce a functional protein), there was no relevant category to select from to describe this therapy during the submission process, and they were forced to select “gene therapy” as the closest available term.

These examples illustrate instances where RNA and gene therapies have become conflated, despite there being clear and important differences between these 2 therapeutic approaches. For instance, the temporary versus permanent states of RNA and DNA, respectively, have important implications for the durability associated with RNA and gene therapies in the treatment of genetic diseases. Gene therapy is often considered a “one-and-done” therapy, where only a single dose is required for lifetime efficacy. Conversely, RNAi therapies and RNA-editing approaches require repeated dosing, albeit less frequent than traditional pharmacotherapies, due to the continual production of the mRNA they act on.

Furthermore, RNA and gene therapies tend to utilize different delivery methods, with RNA therapies more likely to be delivered via non-viral delivery systems. This is important because delivery methods have the potential to impact the cost, tolerability, and efficacy of a treatment, as well as regulatory requirements. While some RNA therapies, such as RNAi therapies, are regulated as small-molecule drugs under a New Drug Application, gene therapies that use viral vector delivery systems and mRNA vaccines are regulated as biological drugs under a Biologics License Application).

Why is this important?

As of Q3 2024, 32 gene therapies and 34 RNA therapies have been approved, while 2068 gene therapies and 1217 RNA therapies are currently in pipeline development. As more gene therapies and RNA therapies become available, it is important that treating physicians and patients fully understand the treatment they are prescribing and receiving.

However, data suggests that many physicians have limited understanding of RNA and gene therapies and their differences. In a survey conducted in September 2019 by InCrowd, around half of screened participants considered RNAi, siRNA, ASO, and mRNA to be gene therapies and many were unfamiliar with these terms.

The spread of medical misinformation amongst the public is another point of concern. As an example, a survey conducted in July 2024 by the Annenberg Public Policy Center of the University of Pennsylvania found that 15% of respondents incorrectly believed that COVID-19 vaccines can alter human DNA.

The concept of informed consent in healthcare requires patients to understand the risks, benefits, and potential alternatives of a given therapeutic intervention. As the benefits and risks differ between gene therapy and RNA therapy, it is important that patients understand these differences. Yet patients tend to receive information from their healthcare professionals and the internet, and neither source may be completely reliable on this topic at present.

What is the solution?

We need the medical and scientific community to come together to agree clear terminology and lexicon to describe and differentiate between advanced therapies such as gene and RNA therapies, so that we can begin speaking the same language. The American and European societies of gene and cell therapy (ASGCT and ESCGT, respectively) are well poised to lead this effort and promote widespread adoption of recommended terms.

There is also a clear need for medical education and training for medical professionals to familiarize them with different types of advanced therapies and to ensure that they are comfortable and confident in explaining these therapies and how they work to patients. In an age of fake news and misinformation, it is imperative that healthcare professionals are equipped with the knowledge and tools to debunk myths and misbeliefs in relation to RNA and gene therapies.

And finally, patients would benefit from more emphasis being placed on the development of plain-language summaries and other forms of communication aimed at non-scientific audiences, funded by the developers of these current and emerging therapies and made freely accessible to broader audiences than just specialist HCPs.