CRISPR may be a Nobel Prize winning discovery, but its translation into a therapeutic use raises many questions on safety, edit specificity and their consequences. In CRISPR, a short RNA (guide RNA) navigates the Cas enzyme to make the edit in the right place, and this gRNA plays a critical role in safety. Helex’s novel platform is advancing the design, in vitro validation and manufacturing of therapy grade synthetic gRNAs to accelerate drug developers to enhance safety of their therapies. 

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We spoke with CEO Poulami Chaudhuri, Ph.D., about a future without genetic disease. 

What is the mission of Helex Bio?

The mission of Helex is to drive synthetic guide RNA driven therapeutics to solve for rare genetic conditions by partnering with drug developers. Safety is one of the biggest challenges in translating promising technologies like CRISPR into workable therapies, and we want to contribute to making gene editing safer, ultimately accelerating these therapies to market. 

What inspired you to found Helex? 

I have experienced firsthand the advancement of science from a genetics perspective to be able to accurately read the genetic code and understand its consequences on human life. It is extremely inspiring to see how we have moved from accurately reading the code to holding the potential to actually solve for these conditions. 

As a new mother, I wanted to apply my extensive experience in the space of genetics, molecular biology and bioinformatics to contribute to alleviating the pain undergone by those who suffer from rare genetic conditions that until now have had no real solutions. 

What is the key to developing safer CRISPR-based gene therapies?

To develop safer CRISPR-based gene therapies, it is critical to deepen our understanding of the core cellular and tissue mechanisms, and thus to understand the impact of making a DNA edit on all aspects of these cell and tissue mechanics. 

While science has come a long way, the specificity of edits and its consequences of off-targets needs to be better understood and defined. The human body is complex, and every edit has a unique and significant impact. This impact has to be uncovered at many dimensions to make these therapies safer. 

How does Helex create safer therapies?

Helex is the GPS for gene editing. We look at the entire design of guide RNA from a three dimensional, four dimensional perspective. We have an AI-based modular platform that makes the most precise guide RNAs which are gene, cell & tissue specific. 

Today one of the biggest challenges for performing gene therapies within the body, or in vivo, is the unintended tissue effects. So while the entire field is working towards vector innovation and development, at Helex, we are designing tissue-specific guide RNAs. These tissue-specific guide RNAs act as an extra layer of safety even when there is a leaky expression by the vector.

What does it mean to design guide RNA from a 3D or 4D perspective?

At Helex, we are advancing this science using the principles of epigenetics which states that structure defines function. Every cell functions differently, and the epigenetics vary between cell types. 

Our platform informs guide RNA design keeping in mind these core principles, and are catered to every cell/ tissue type to make them extremely specific. This is especially pertinent when we talk about in-vivo or inside the body editing. 

In addition, we do a very detailed safety characterisation of the edits at the genotypic, phenotypic level, and keeping in mind the impact on the target gene and all other genes associated with it. This is the 3D/ 4D holistic approach that we take. 

How will you work with other cell & gene therapy companies? 

We intend to be a lead guide RNA optimizing partner for drug developers, where we custom design gRNAs using our platform and based on their therapeutic modality. We will validate  and characterize these gRNAs as drug substances and ultimately synthesize them for the drug developers. 

What keeps you motivated to bring your product to market? 

Complete strangers reach out to us on social media platforms like LinkedIn and give us encouragement because they have a loved one that is suffering from one of these conditions, and express their hope for these therapies to see the light of the day. We feel a sense of purpose and inspiration despite the surmounting challenges.