Shape Therapeutics is a biotechnology company focused on developing advanced genomic medicines. Established in 2018, the company leverages an artificial intelligence (AI)-driven platform to create innovative therapeutic solutions. Their primary focus centers on programmable RNA editing technology, which aims to address the root causes of various diseases at a molecular level.
The overarching goal of Shape Therapeutics is to develop curative and transformative medicines by precisely manipulating RNA. This approach differs from traditional gene editing by targeting the RNA molecules, which are temporary copies of genetic instructions, rather than making permanent changes to the DNA itself. By doing so, the company seeks to correct genetic errors and modify cellular processes without altering the body’s permanent genetic blueprint.
The company’s technology engages natural cellular machinery within the human body to achieve its therapeutic effects. This strategy allows for a novel form of genetic medicine that is highly precise and potentially reversible. Shape Therapeutics has garnered substantial investment and formed strategic partnerships with major pharmaceutical entities, highlighting its RNA-focused platform’s potential.
How Shape Therapeutics Works
Shape Therapeutics employs a sophisticated RNA editing platform, known as RNAfix, to precisely modify genetic instructions at the RNA level. This technology harnesses the power of naturally occurring enzymes within human cells called Adenosine Deaminases Acting on RNA, or ADARs. These ADAR enzymes are ubiquitous in the body and possess an inherent ability to convert adenosine (A) nucleotides into inosine (I) within double-stranded RNA molecules.
The core of Shape Therapeutics’ approach lies in guiding these endogenous ADAR enzymes to specific target sites on messenger RNA (mRNA). They achieve this through the use of engineered guide RNAs (gRNAs). When introduced into a cell, these custom-designed gRNAs are complementary to a specific segment of the target mRNA. Upon binding, they form a double-stranded RNA structure, which then acts as a recognition signal for the ADAR enzyme.
Once the ADAR enzyme is recruited to this specific double-stranded RNA region, it catalyzes the conversion of adenosine to inosine. The cellular machinery responsible for protein synthesis interprets inosine as guanosine (G). This A-to-I conversion effectively “rewrites” a specific point in the RNA sequence, leading to a change in the resulting protein without altering the original DNA blueprint. For instance, a disease-causing mutation that leads to a faulty protein can be corrected at the RNA level to produce a functional one.
To ensure the precision and efficiency of this editing process, Shape Therapeutics utilizes advanced artificial intelligence models, such as DeepREAD. These AI tools are trained on vast datasets of RNA sequences and experimental editing outcomes, allowing them to predict and design optimal gRNA structures. This computational power enables the creation of gRNAs that are highly specific to their targets, minimizing unintended edits and maximizing therapeutic effect.
The delivery of these engineered gRNAs into target cells is typically facilitated by adeno-associated viruses (AAVs). These modified viruses act as safe and efficient carriers, delivering the genetic instructions for the gRNAs to the desired tissues or organs. The AAV-mediated delivery allows for sustained production of the gRNAs within the cells, providing a durable therapeutic effect without the need for frequent re-administration.
Diseases Targeted by Shape Therapeutics
Shape Therapeutics is directing its innovative RNA editing technology toward a broad spectrum of diseases, particularly those with a clear genetic basis. A significant area of focus for the company is neurological disorders. This includes debilitating conditions such as Alzheimer’s disease, Parkinson’s disease, and Rett syndrome, where correcting specific genetic errors at the RNA level can mitigate disease progression or symptoms.
For instance, in Parkinson’s disease, Shape Therapeutics is exploring targets related to LRRK2 mutations, known genetic contributors to the condition. In Rett syndrome, their efforts concentrate on correcting the R168X mutation in the MECP2 gene, highlighting their precise approach to specific genetic defects. The ability to deliver these RNA-based therapies effectively to the brain via advanced viral vectors makes their platform suitable for these complex central nervous system disorders.
Beyond neurological conditions, the company is also targeting various ocular diseases. This includes ABCA4-related diseases, which encompass inherited retinal degenerations like Stargardt disease and certain forms of retinitis pigmentosa. The precise RNA editing capability offers a way to address the genetic defects underlying vision loss in these conditions.
The versatility of Shape Therapeutics’ platform allows it to consider a wide array of other rare genetic disorders where a single-nucleotide change or a specific protein modification can have a profound therapeutic impact.
The Unique Promise of Shape Therapeutics
Shape Therapeutics’ approach to genetic medicine offers distinct advantages compared to other therapeutic modalities, such as traditional small molecule drugs or DNA gene editing. A primary differentiator is its ability to modify RNA without making permanent alterations to the patient’s DNA. This avoids the potential risks associated with irreversible genomic changes and unintended DNA mutations, which can be a concern with DNA-targeting technologies.
The transient nature of RNA, which naturally degrades over time, means that RNA edits are also temporary. This provides a valuable element of reversibility and tunability to the therapy. For conditions where continuous or precise modulation of protein levels is required, or where a permanent genetic change might be undesirable, RNA editing offers a flexible solution that can be adjusted or even halted if necessary.
Leveraging the body’s own ADAR enzymes, which are naturally present in human cells, contributes to a potentially favorable safety profile. This strategy minimizes the introduction of foreign proteins that could trigger unwanted immune responses, a challenge sometimes encountered with other gene-editing platforms. The inherent biological compatibility of the system is an important aspect of its unique promise.
The sophisticated AI-driven design of guide RNAs allows for exceptional precision and specificity in targeting. This advanced computational capability helps ensure that edits occur at the intended RNA sequences, minimizing off-target effects and maximizing therapeutic efficacy. The precise control over the editing process enables the potential to address a broad spectrum of genetic mutations by directly correcting the flawed RNA message.