Oligos, mRNA, Or Gene Editing: Where Should You Bet?

By William Soliman, Ph.D., BCMAS, founder & CIO, White Manna Capital

In his first two installments of Soliman Says, William Soliman, Ph.D., BCMAS, explored the forces reshaping biotech: from the rise of RNA as a therapeutic class to the capital dynamics driving innovation across the industry. In this third column, he turns to a more pointed question: how should investors, operators, and strategists think about allocating bets across the three most powerful modalities redefining modern medicine?

At a moment when biology is increasingly programmable, the conversation is no longer about whether these technologies work; it is about where, when, and how they will create value. Oligonucleotides, mRNA, and gene editing each represent a distinct layer of intervention, with different timelines, risk profiles, and degrees of clinical and commercial validation.

Here, Soliman moves beyond broad trend analysis and into strategic positioning — unpacking what each modality offers today, where the bottlenecks remain, and how to think about opportunity across a rapidly converging therapeutic landscape.

The Next Wave Of Value

The last decade in biotechnology has been defined by a fundamental shift. We are no longer just discovering drugs. We are programming biology. At the center of this shift are three powerful modalities: oligonucleotide therapeutics, mRNA platforms, and gene editing technologies.

Each represents a different layer of biological intervention. Each carries its own risk and reward profile. And each is competing not just scientifically but for capital, talent, and strategic prioritization across pharma and biotech.

So where should you bet?

The answer is not about picking a single winner. It is about understanding where each modality sits in its maturity curve, how scalable it is, and where the next wave of value creation will come from.

The Case For Oligonucleotides: Quiet Execution, Real Revenue

Oligonucleotide therapeutics, including antisense and siRNA approaches, are often overlooked in favor of flashier technologies. This category has become one of the most commercially validated RNA based modalities in medicine.

Companies like Ionis Pharmaceuticals and Alnylam Pharmaceuticals have built strong platforms with approved therapies targeting rare and specialty diseases. These drugs work by modulating gene expression, turning genes off or altering RNA splicing without permanently modifying DNA.

What makes this space compelling is its predictability. Regulatory pathways are clearer, repeat dosing supports recurring revenue, and expansion into areas like cardiometabolic disease is already underway. This makes mRNA technology more than just theoretical science and more operationalized biology with commercial traction.

That said, oligonucleotides are not without constraints. Delivery remains a challenge outside liver targeted applications, and while the science is validated, the upside tends to be more evolutionary than revolutionary. From an investment perspective, this is the segment that behaves most like a traditional pharmaceutical business. It compounds steadily, de-risks earlier, and rewards execution.

mRNA: From Breakthrough To Proving Ground

mRNA moved from scientific promise to global validation almost overnight during the COVID 19 pandemic. Vaccines developed by Moderna and Pfizer in partnership with BioNTech demonstrated what is possible when speed, scale, and biology converge.

The core idea is powerful. Instead of manufacturing therapeutic proteins externally, you deliver instructions that enable the body to produce them internally. Now the market is asking a more difficult question. Was this a unique moment driven by a global pandemic, or is mRNA a durable and scalable platform across multiple disease areas?

There are clear advantages. The speed of design and manufacturing is unmatched. The platform is highly adaptable. And there is growing momentum in oncology, particularly in personalized cancer vaccines. At the same time, limitations are becoming more apparent. Questions remain around durability of expression, tolerability, and the ability to extend beyond vaccines into chronic disease settings.

The next phase of mRNA will not be defined by hype. It will be defined by whether companies can demonstrate consistent clinical success outside infectious disease. If they can, this becomes one of the most scalable platforms in biotech. If not, it risks being viewed as a powerful but narrow tool.

Gene Editing: High Risk, Asymmetric Upside

Gene editing sits at the far end of the spectrum. It is the most ambitious of the three and potentially the most transformative.

Technologies such as CRISPR based systems developed by companies like CRISPR Therapeutics and Editas Medicine are designed to permanently alter DNA. This opens the possibility of one-time treatments that could potentially cure genetic diseases, elimination of lifelong therapy, and  a complete redefinition of how we think about chronic illness. Recent approvals in sickle cell disease have moved gene editing from concept to clinical reality. That milestone alone has shifted investor perception. But the risks remain significant. Delivery to specific tissues is still a major hurdle. Safety concerns, particularly off-target effects, require long-term validation. Manufacturing and cost structures are complex. And regulatory frameworks are still evolving.

This is not a space for incremental thinking. It is a space where outcomes are binary. Either these technologies fulfill their promise and redefine medicine, or they face setbacks that slow adoption for years.

From a capital allocation standpoint, gene editing represents asymmetric upside. It carries higher risk, but the magnitude of potential return is unmatched.

So Where Should You Bet?

The most sophisticated investors are not choosing one. They are positioning across all three based on time horizon and risk tolerance. Here’s how to think about it. Oligonucleotides offer near-term visibility and commercial durability. They are the foundation. They generate revenue and validate RNA as a therapeutic class. mRNA sits in the middle. It has already proved it can work at scale but now must demonstrate breadth. The upside is significant if it expands successfully into oncology and beyond.

Gene editing represents the frontier. It is where the largest breakthroughs and the largest risks coexist. This is where long-term, high-conviction capital is being deployed by savvy investors. The deeper insight is this: these modalities are not mutually exclusive. They are converging. The future of medicine will not be defined by a single platform. It will be defined by how these technologies are integrated, layered, and applied to increasingly complex diseases.

The real bet is not just on oligos, mRNA, or gene editing. It is on the companies that understand how to use them together. One final thought: the recent collaboration between Eli Lilly and Insilico Medicines leveraging AI technology represents an interesting twist to the drug development story and may certainly have longer-term implications for oligo-based drugs.

About The Author:

William Soliman, Ph.D., is the founder & CEO of the Accreditation Council for Medical Affairs (ACMA) and the founder & CEO of White Manna Capital Partners, a biotech/pharma focused hedge fund. The ACMA is the leading life sciences accreditation, certification, and training company in the world and established the first ever certification standards for prior authorization, reimbursement, pharma sales, medical science liaisons, and medical affairs professionals. Soliman is considered a pharmaceutical industry futurist. In March 2021, he testified before the United States Congress’ Energy and Commerce Health Subcommittee about the pharmaceutical industry and the importance of professional standards for those who directly engage healthcare providers, like sales representatives. Soliman is a former pharmaceutical executive who held leadership roles at several Big Pharma companies, including Merck, Johnson & Johnson, AbbVie, and Gilead. He is routinely featured on media outlets such as NewsNation, Fox News, ABC News, Forbes, Al Jazeera, Yahoo! Finance, Yahoo! Business TV, and more. Soliman received his Ph.D. from Columbia University and his bachelor’s degree from New York University.