Precision Delivery in the Neuroplastogen Era: How the Deliverome Project is Mapping the Future of CNS Therapeutics

By Sasha Stafford, Principal Scientist & Founder, Prodelic Technologies LLC

The psychedelic biotechnology sector is currently navigating a critical inflection point. As the industry pivots from studying first-generation classic psychedelics to engineering second- and third-generation neuroplastogens—compounds designed to drive rapid neural plasticity without the hallucinogenic burden—the core scientific challenge has shifted. Today, the primary hurdle is no longer mere molecule discovery; it is targeted delivery.

Identifying a small molecule that can regrow dendritic spines or promote synaptogenesis is a remarkable achievement. However, ensuring that therapeutic payload reaches highly specific neuronal populations without triggering systemic off-target toxicities (such as 5-HT2B-mediated valvulopathy) remains a persistent bottleneck in central nervous system (CNS) drug development.

A newly launched initiative, the Deliverome Project, promises to systematically dismantle this bottleneck. Backed by the Hertz Foundation, the Astera Institute, and operating as a Focused Research Organization (FRO), Deliverome aims to construct the first comprehensive, open-access atlas of human cell-surface proteins.

For developers in the psychedelic and neuroplastogen space, this ambitious undertaking could fundamentally alter how we approach rational drug design, target validation, and intracellular pharmacokinetics.

The Delivery Bottleneck in Modern Neuropharmacology

In targeted drug development, cell-surface proteins act as molecular addresses. While surface proteins account for only 15% to 20% of the proteins in the human body, they are the targets for over 60% of approved drugs due to their accessibility to biological medicines, antibodies, and engineered nanocarriers.

However, mapping these proteins is fraught with technical hurdles. Surface proteins are notoriously difficult to quantify—they are often present at low abundance, their expression varies drastically depending on cell state, and many are rapidly internalized and recycled. Consequently, biopharma researchers lack a standardized reference for which proteins decorate specific cell types, and more importantly, which of those proteins function as active gateways into the cell's interior.

As Becca Carlson, co-founder of the Deliverome Project and former Flagship Pioneering associate, noted upon the project's launch, there is a gaping void between our growing ability to identify disease targets and our limited capability to deliver medicines strictly to those defined cell populations.

Enter Deliverome: Mass Spectrometry Meets Machine Learning

The Deliverome Project, co-founded by Carlson and biochemist Bobby Hollingsworth, is stepping into this void with a five-year roadmap and a $5 million seed investment. Structured as an FRO—a model designed by Hertz Fellows Sam Rodriques and Adam Marblestone to tackle infrastructure-scale scientific challenges—the project will circumvent the traditional, siloed academic publication cycle by continuously releasing its findings as open-access "micro-publications."

To build the atlas, the Deliverome team is developing proprietary proteomics workflows that combine high-throughput mass spectrometry with functional genomics. This dual approach will allow them to quantify membrane-associated proteins while simultaneously using genomic perturbations to test how effectively these receptors mediate intracellular uptake.

Crucially, the resulting datasets are being structured specifically for computational drug discovery. Machine learning models will be deployed to analyze the complex relationships between cell types, receptor abundance, cargo properties, and intracellular routing outcomes—transforming what is currently a years-long process of trial-and-error R&D into a predictable, engineered workflow.

Strategic Implications for Neuroplastogen Development

For companies operating in the psychedelic and psychoplastogen verticals, the Deliverome atlas offers a strategic blueprint for the next decade of CNS drug delivery. The data generated by this project will directly impact three crucial areas of industry R&D:

1. Engineering Tissue-Specific Localization (Bypassing Systemic Toxicity)

A major gating factor for the commercial viability of novel psychedelic derivatives is off-target receptor activation. A neuroplastogen may need to act on cortical pyramidal neurons to treat treatment-resistant depression, but circulating systemically, it may bind to receptors in the heart, gut, or immune system.

By querying the Deliverome atlas, medicinal chemists and delivery engineers could identify cell-surface proteins uniquely enriched on targeted neuronal subtypes. Biologics, nanoparticles, or antibody-drug conjugates (ADCs) could then be engineered to bind exclusively to these distinct molecular addresses, ensuring the therapeutic accumulates only in the target tissue. This precision localization dramatically broadens the therapeutic window and de-risks clinical pipelines by mitigating systemic adverse events.

2. Unlocking Intracellular Targets for Neuroplasticity

Perhaps the most significant paradigm shift in recent psychedelic science is the revelation regarding intracellular receptor activation. Recent seminal research suggests that while activating surface-level 5-HT2A receptors drives hallucinations, it is the activation of intracellular 5-HT2A receptors that specifically promotes therapeutic neuroplasticity and dendritic arborization.

This makes intracellular delivery an absolute imperative for next-generation neuroplastogens. Deliverome’s mission aligns perfectly with this mandate. The project is not merely cataloging what sits on the cell membrane; it is mapping receptor-mediated endocytosis. By identifying which receptors fold inward to form vesicles, and tracking whether they route their cargo to degradation compartments or to the cytoplasm and nucleus, Deliverome will provide developers with the exact cellular "doorways" needed to ferry neuroplastogens across the lipid bilayer and directly to their intracellular targets.

3. Accelerating Precision Medicines for Rare Neurological Disorders

The current commercial landscape often forces biotechs to focus on broad psychiatric indications with massive total addressable markets (TAMs), simply to justify the exorbitant costs of R&D and delivery optimization. Deliverome’s open-access model drastically lowers this barrier to entry.

For boutique biotechs exploring neuroplastogen interventions for rare, genetically defined neurological disorders, the atlas will eliminate the need to build bespoke targeting mechanisms from scratch. Developers will have access to a repository of functional surface proteins and their internalization dynamics, allowing for the rapid vectorization of existing molecular assets toward rare disease populations.

A Catalyst for Rational Design

As the Deliverome Project spins up its laboratory operations and begins hiring experts in functional genomics and proteomics, the broader biotechnology sector should be preparing to integrate its findings.

For the psychedelic industry, the era of relying solely on broad-spectrum, systemic administration is drawing to a close. Here, at Prodelic Technologies, we believe the future belongs to rationally designed therapies that hit the right receptor, on the right cell, in the right intracellular compartment. By making the human surfaceome measurable, comparable, and openly accessible, the Deliverome Project is poised to provide the exact map the industry needs to navigate this new frontier.