Our portfolio
Sanford Labs maintains an active portfolio of research projects across our five program areas. Each project is designed with clear translational goals and defined milestones — advancing to the point where promising science can move into clinical development.
Science OverviewProgram: Enhancing protein expression and activity
Disease area: Neurofibromatosis type 1 (NF1)
Neurofibromatosis type 1 (NF1) is a genetic disorder caused by loss-of-function mutations in one copy of the NF1 gene, which encodes neurofibromin — a tumor suppressor that regulates cell growth. Patients retain one functional gene copy, but reduced neurofibromin levels are insufficient to maintain normal cell regulation, leading to uncontrolled cell growth, tumor formation, and a range of neurological and developmental symptoms. There are currently no disease-modifying treatments.
Our strategy
Project Acadia has developed oligonucleotide-based strategies to overcome NF1 haploinsufficiency, identifying lead candidates through integrated molecular and functional screening for RAS signaling restoration in disease-relevant cell models. This approach has the potential to reduce tumor burden and improve neurological outcomes.
Acadia:
Disease-modifying therapy for NF1
Status:
Lead candidate selection
Disease area: Dravet Syndrome
Dravet Syndrome is a rare, severe developmental and epileptic encephalopathy with symptoms often emerging in infancy. The disease is caused by loss-of-function variants in one copy of the SCN1A gene, which disrupts the balance of excitation and inhibition in neural circuits and leads to frequent, difficult-to-control seizures. Over time, many patients develop additional challenges including developmental delay, cognitive and behavioral comorbidities, motor impairment and an elevated risk of status epilepticus and sudden unexpected death in epilepsy (SUDEP), underscoring the need for more effective disease-modifying therapies.
Our strategy
Project Mammoth Cave is developing antisense oligonucleotides (ASOs) designed to increase SCN1A expression by relieving translational repression. Rather than modulating mRNA splicing, this approach targets repressive regulatory elements in the SCN1A transcript to “de-repress” protein production from the remaining functional allele. By boosting protein expression levels, we hope to restore excitation–inhibition balance and deliver clinically meaningful improvements in seizure burden and related outcomes. This approach of increasing protein expression levels by relieving translational repression could also be applied to other developmental and epileptic encephalopathies and other diseases
Mammoth Cave:
Oligonucleotides to treat Dravet Syndrome
Status:
Lead candidate selection
Program: Building bifunctional RNA therapeutics
Disease area: Cancer, neurodegenerative disease, neuromuscular disease
Targeting RNA with small molecules has attracted increased interest in recent years. This strategy was powerfully validated by the drug Evrysdi (risdiplam), which treats spinal muscular atrophy (SMA) by modulating RNA splicing. Efforts have also been made to target mRNAs that encode proteins such as Huntingtin for Huntington’s disease and MYC for various cancers. A major challenge in these approaches, however, is that small molecules that bind to an mRNA often fail to significantly alter protein expression.
Our strategy
Project Arches seeks to discover and develop small molecules that selectively engage RNA effectors — proteins that impact RNA stability, ribosome engagement and related functions. Inspired by PROTACs (proteolysis targeting chimeras), which control protein levels by linking targeting molecules to protein effectors, our approach endows RNA-binding compounds with defined, programmable functions. By combining our RNA effector binders with diverse RNA-targeting compounds, we seek to precisely modulate protein expression and cellular pathways, addressing unmet needs in cancer, neurodegeneration and neuromuscular diseases. This strategy offers targeted intervention without altering the genome or relying on gene editing.
Arches:
Recruiting RNA effectors using small molecules
Status:
Performing structure-activity relationship analysis on lead candidates for multiple RNA effectors;
Open to partnering discussions
Program: Targeting RNA-binding proteins
Disease area: Neurodegenerative disease, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
ALS and FTD are devastating neurodegenerative diseases with few effective treatments. A defining feature of both conditions is the abnormal behavior of TDP-43, an RNA-binding protein that normally resides in the nucleus and regulates the splicing, stability and transport of mRNAs encoding numerous proteins that are crucial for neuronal function. In affected neurons, TDP-43 mislocalizes to the cytoplasm, where it forms toxic aggregates — simultaneously depleting the nucleus of a protein it needs to function and burdening the cell with inclusions it struggles to clear.
Our strategy
Project Saguaro has identified a novel target protein, downregulation of which preserves essential nuclear TDP-43 functions while blocking the formation of toxic cytoplasmic aggregates in human cell−based disease models. Project Saguaro is pursuing antisense oligonucleotide (ASO) and small interfering RNA (siRNA) approaches to identify candidates for potent, selective and safe downregulation of this target protein.
Saguaro:
Restoring TDP-43 functionality to treat neurodegenerative disease
Status:
Development candidate selection;
provisional patent application filed
Disease area: Cancer, metabolic disease, immune disorders
The emerging concept of riboregulation reveals that RNA can directly modulate protein function — for example, through the allosteric inhibition of metabolic enzymes like Enolase 1 or the scaffolding of energy-regulating complexes like AMP-activated protein kinase (AMPK). This regulatory layer is increasingly implicated in the development of various cancers, metabolic diseases like diabetes, and immune disorders, where the sequestration of proteins into pathological stress granules or the loss of RNA-mediated control drives cellular dysfunction. Consequently, the RNA-binding surfaces of thousands of "unconventional" RNA-binding proteins are now being explored as high-value, druggable targets for translational medicine.
Our strategy
Project Badlands is assessing multiple potential targets using key criteria, including their validation in disease pathology, known or anticipated safety and toxicity risks, technical feasibility and market opportunity relative to competing approaches. As a proof of concept, we have performed a DNA-encoded library (DEL) screen to identify small molecule binders to a well-characterized riboregulatory target. Promising lead candidates are undergoing secondary assays to confirm both binding activity and functional impact.
Badlands:
Therapies targeting RNA-protein interactions
Status:
Target discovery and lead candidate screening
Program: In vivo mRNA therapeutics
Disease area: Respiratory infectious diseases
Respiratory viruses such as influenza, RSV and other emerging viruses remain a major global health burden, particularly for vulnerable populations where vaccines may be less effective or too slow to deploy. While prophylactic monoclonal antibodies provide immediate protection, their use is constrained by high systemic dosing and limited durability. Delivering protective biologics directly to the respiratory tract presents an opportunity to achieve rapid, localized immunity with improved efficiency.
Our strategy
Project Mesa Verde is developing an in vivo mRNA-based approach to enable localized expression of prophylactic monoclonal antibodies in the lung. Using lung compatible lipid nanoparticles (LNPs) for delivery, mRNA-encoded antibodies are expressed in vivo at the primary site of viral entry.
This approach aims to achieve high local exposure with lower doses, enabling rapid onset and improved pharmacokinetics. Core efforts focus on engineering mRNA for stability and efficient translation, alongside LNP systems optimized for airway delivery and pulmonary cell uptake. The platform is designed for both seasonal and outbreak-driven prophylaxis, with the flexibility to rapidly encode antibodies against emerging threats.
Mesa Verde:
Lung-expressed mAb therapeutics for respiratory virus prophylaxis
Status:
Evaluating efficacy of lung-expressed mAbs in vivo
Disease area: Infectious disease, cancer, metabolic disorders, cardiovascular disease
Full-length RNA therapeutics, specifically mRNA and circular RNA (circRNA), are rapidly advancing as vaccines for infectious diseases such as COVID-19, influenza and RSV, as well as personalized cancer vaccines targeting neoantigens in melanoma and glioblastoma. Beyond vaccination, these platforms serve as protein replacement therapies for rare metabolic disorders like propionic acidemia (PA) and methylmalonic acidemia (MMA) by delivering the genetic instructions for missing enzymes. Emerging applications include in vivo generation of CAR-T cells using mRNA-lipid nanoparticles, enabling treatment of cardiac fibrosis and hematologic malignancies without the complexities of ex vivo cell engineering. Additionally, the enhanced stability of circRNA is being leveraged to achieve more durable expression for gene-corrective therapies in chronic and autoimmune diseases.
Our strategy
Project Haleakala is developing RNA-based aptamers to enhance the performance of RNA therapeutics. Aptamers — short nucleotide sequences that bind specific targets — are designed here primarily to engage proteins involved in RNA stability or translation. Our work includes both optimizing existing aptamers and identifying new sequences that recruit key RNA effectors. These aptamers are engineered for compatibility with common nucleoside modifications, such as 1-methylpseudouridine (1mePU), which reduces immunogenicity and, when incorporated throughout the RNA, streamlines manufacturing and lowers costs.
Haleakala:
Enhancing RNA therapeutics
Status:
Optimizing first-generation 1mePU aptamers;
Open to partnering discussions
Program: RNA design by AI and machine learning
Disease area: Infectious disease, cancer, autoimmunity, cardiovascular disease, genetic disorders
RNA therapeutics are poised to transform treatment across a broad spectrum of diseases. Their most prominent recent success is the rapid deployment of prophylactic vaccines for SARS-CoV-2. In addition, numerous late-stage clinical trials are evaluating mRNAs that encode personalized neoantigens in cancer such as melanoma and lung cancer. Beyond oncology, RNA therapeutics can direct the intracellular production of missing enzymes for inborn errors of metabolism, including propionic acidemia. They also hold promise in autoimmune diseases, such as multiple sclerosis, where engineered mRNAs can retrain the immune system to achieve antigen-specific tolerance. The high programmability of mRNA allows for emerging applications in regenerative medicine, including heart tissue repair and in vivo gene editing for hereditary disorders.
Our strategy
Project Sequoia is creating an AI-powered RNA design platform to help make RNA medicines more effective and more predictable in the tissues where they are needed most. By integrating machine learning with experimental validation, we model how RNA sequence features influence key performance factors, such as RNA structure, stability and translation efficiency across different cellular contexts. These insights guide the design of sequences that achieve precise levels and durations of therapeutic protein expression, while prioritizing safety and manufacturability. This approach has the potential to broaden the capabilities of RNA therapeutics across multiple disease areas, from genetic disorders to cancer and immune-mediated diseases, by improving consistency, tolerability and clinical impact.
Sequoia:
Universal RNA sequence design by AI/ML
Status:
Fine-tuning model performance;
Open to partnering discussions
