At a recent medical conference, scientist and Harvard professor George Church presented an argument causing anxiety among healthcare investors: The days of CRISPR gene editing might be numbered. He called CRISPR a "blunt ax" and said "it's called editing, I think it's really genome vandalism." Church made the case that the biotechnology industry might be better off moving beyond cutting genomes and toward more precise gene-editing techniques. 

The words carry significant weight because Church was integral to the commercialization of CRISPR gene-editing tools. He's a co-founder of Editas Medicine (NASDAQ:EDIT), and he led work on other gene-editing and gene-writing technologies most people have never heard of. These criticisms raise the question: If other gene-editing tools are about to eat CRISPR's lunch, what does it mean for companies such as Editas Medicine, Crispr Therapeutics (NASDAQ:CRSP), and Intellia Therapeutics (NASDAQ:NTLA)?

A pair of golden scissors.

Image source: Getty Images.

Drawbacks of CRISPR technologies

CRISPR tools are often referred to as genetic scissors, owing to their potential to cut genomes at specified locations. It turns out, all of that cutting can also create problems.

While several gene-editing tools cut DNA in an attempt to remove faulty sequences, CRISPR relies on DNA repair mechanisms present inside cells to stitch the genome back together. When the repair mechanisms are defective, the cell loses an important check on its growth cycle and can fail to stop opportunistic cancer cells from proliferating. While it's inaccurate to say CRISPR causes cancer, the gene-editing tool has been shown to provide cancer an assist in certain cases. 

In addition to the problem caused by cutting DNA without engineering a repair, it turns out that CRISPR isn't as specific in human cells as the media narrative suggests. The "blunt ax" can make edits to a genome far away from the target site, resulting in unintended alterations to the genome.

A woman in the background and a DNA model in the foreground.

Image source: Getty Images.

Will these gene-editing technologies replace CRISPR?

Church's comments reminded the audience that gene editing isn't magic, which can be easy to forget given the media hype surrounding CRISPR. His argument closely tracks a 2017 paper that laid out the seven characteristics harbored by an ideal gene-editing system. Therefore, it makes sense that the future of precise gene editing may be divided among multiple systems that each thrive in specific applications.

In multiple recent speaking engagements, Church laid out four different gene-editing systems that may move the field "beyond cutting" for applications as diverse as industrial biotechnology, human medicine, and xenotransplantation, which is the process of grafting or transplanting organs or tissues between members of different species.   

Gene-Editing System

Advantages

Cell Types

Lambda-red recombinase

Allows direct modification of genomes resulting in fast turnaround times and few experimental steps. Used in "recombineering."

Prokaryotes (bacteria)

Phage integrases

Simple method to make precise and controlled edits; also repairs sliced DNA without using cell's repair mechanisms.

Prokaryotes (bacteria) and eukaryotes (mammals)

TAL deaminases

The basis for base editing, which converts DNA base pairs in place without cutting the genome.

Prokaryotes (bacteria) and eukaryotes (mammals)

Chemical targeting

Engineering enzymes and proteins (including in the systems above) for direct genome modification without cutting DNA.

Prokaryotes (bacteria) and eukaryotes (mammals)

Data source: George Church, scientific literature.

What does this mean for beloved CRISPR stocks? Well, investors aren't yet concerned with precise gene editing of bacteria or plants, so those applications aren't top of mind for now, so we can set aside lambda-red and the use of recombineering for the time being. Meanwhile, chemical targeting systems include a broad range of techniques that can be combined with other systems.

That leaves two competing technologies insofar as investors are concerned: phage integrase systems and base editing. Both systems check more boxes on Church's list of characteristics for an ideal gene-editing system than CRISPR does. Both are considered ideal candidates for in vivo and ex vivo. Importantly, both avoid triggering the problematic DNA repair mechanisms observed in some uses of CRISPR.

Base editing will provide the most immediate test. The gene-editing system is being leveraged by startup Beam Therapeutics, which shares technology and founders with Editas Medicine. While it hasn't publicly announced its top preclinical candidates, analysts will be closely watching the company's development in the next few years and comparing its approach to that of the pioneers.

A yellow arrow opposing the direction of many white arrows.

Image source: Getty Images.

CRISPR isn't a slam-dunk

The fact that CRISPR isn't an ideal gene-editing technology isn't exactly news among scientists, but Church's pointed criticism should remind investors not to get carried away. The mere existence of diverse gene-editing technologies doesn't necessarily pose a threat to Editas Medicine, Crispr Therapeutics, or Intellia Therapeutics. However, the fast pace of innovation is simultaneously the lifeblood of biopharma fortune and an omnipresent reminder that breakthroughs are often unfairly short-lived.

If one of the three CRISPR pioneers encounters clinical failure -- an inevitable reality of the industry -- then it will only heighten the calls for investigating gene-editing systems that go beyond cutting the genome and allow for more precise engineering. With the phage integrases and base editing gene therapy techniques  stepping into the clinic in the next years, investors should leave room for myriad outcomes, favorable or not.

Maxx Chatsko has no position in any of the stocks mentioned. The Motley Fool owns shares of and recommends Editas Medicine. The Motley Fool owns shares of CRISPR Therapeutics. The Motley Fool has a disclosure policy.