Innovation Competition (Boston, MA)

Lipid‐mediated formulation for protein delivery

Concept or business name.
Lipid‐mediated formulation for protein delivery
What general market sector best fits your opportunity?
Please describe the experience and role for key members of this opportunity.
Qiaobing Xu is an Assistant Professor, Department of Biomedical Engineering, at Tufts University. Dr. Xu’s research interests lie at the intersection of material science engineering and chemical biology, with a strong focus on the development of novel biomedical and therapeutic applications. His work is focused on the use of new synthetic materials for the delivery of therapeutic biomacromolecules. During his postdoctoral research with Prof. Robert S. Langer at MIT, Xu synthesized a library of lipid-like molecules, which were tested for efficacy both in vitro and in vivo in the delivery of protein and messenger RNA. Xu is currently developing new drug delivery formulations as a tool to stimulate the host immune system for oncology applications. Xu is also working on developing new micro/nanofabrication techniques for biocompatible materials (e.g. collagen) for tissue engineering applications.
Please describe the key problems your opportunity addresses, such as unmet customer needs, diseases, or other market needs.
Advancements in molecular biology and protein engineering have suggested that proteins that target intracellular biological activities could be potent therapeutics. However, the delivery of proteins safely and efficiently through the cell membrane to reach their intracellular targets remains a challenge. As such, the development of tools for intracellular protein therapies are greatly needed. The nanoparticle drug delivery systems have offered alternative approaches for spatially and temporally controlled protein delivery. A number of synthetic nano-materials including liposomes, polymers, and inorganic nanoparticles have been designed for this purpose. These nanoparticules, however, are still of limited utility for protein therapy due to the low delivery efficiency and/or complicated nanoparticle fabrication processes. Thus, a facile and convenient approach to develop novel nanomaterials for efficient intracellular protein delivery has yet to be developed. The most effective protein delivery system to date, liposomal delivery, has some drawbacks including toxicity problems and formulation difficulties. Surface charge of the liposome is commonly optimized on a protein-by-protein basis, and generally cationic/positive surface charge shows improved interaction with cells; however, highly positive surface charges have been shown to elicit a cytotoxic response. PEGylation modifies the protein therapeutic and could affect the cytotoxicity and efficacy of the drug.
What is the size of the market opportunity addressed by your product or solution?
The protein therapeutics market size is around $60 bln with a 13% growth rate. There are approximately 130 marketed protein therapeutics worldwide. It is currently estimated that there are 25,000-40,000 different genes in the human genome with the majority having functionality inside the cell, yet most protein and peptide pharmaceuticals on the market or under development now achieve their therapeutic effects by targeting cell surface receptor or extracellular domains to initiate a signaling pathway. Viewed from the perspective of therapeutics, intracellular targets represent a tremendous opportunity in terms of harnessing protein/peptide therapeutics to alleviate disease. The field of biological drug development and delivery is evolving at a rapid rate with new drug product formulations being discovered frequently. Liposomes are predicted to reach a market size of $15 billion by 2021. Given the current limitations of liposomal delivery, this new lipid-based composition is expected to achieve an even greater market size, due to its broad applicability across multiple classes of protein and peptide drugs, as well as offering traceless delivery strategies. Targeted drug delivery for cancer treatment is a highly anticipated benefit of nanotechnology-enabled medicine as it allows for more accurate drug delivery than current methods.
Describe your solution or technology and how it addresses the market needs presented above.
We developed a novel and efficient protein delivery platform, using combinatorially designed cationic lipid-based nanoparticles combined with a reversible protein modification approach. In an attempt to strengthen the charge-charge binding of proteins and nanoparticle, we chemically modified the proteins to increase the negative charge density of the protein. Moreover, this chemical modification is responsive to the intracellular microenvironment and could restore the biological function upon reaching the cytoplasm. In effect, this allows the formulation to be broadly applicable across multiples protein and peptide classes, and is not reliant on protein size, net charge, or secondary structure for delivery. Xu’s group has developed a proprietary combinatorial library of cationic lipid-like materials. The new materials have been screened for intracellular protein delivery in a high-throughput manner. The preliminary screening has led to a few candidates and formulations, which showed effectiveness in killing cancer cells both in vitro and in mice models. This novel protein delivery platform will enable the clinical translation of proteins and antibodies as drug candidates by addressing the issue of cell permeability for multiple protein classes. This method will offer a promising cancer treatment where the tumor builds the resistance to small molecule-based drugs.
What is unique about your solution from the technology, intellectual property or business strategy perspectives?
From a technology perspective this solution is unique because it is a platform technology. We have IP for both chemical modification of proteins and lipid-based delivery materials and the intracellular delivery nanoparticle formulation. Based on this portfolio, we are capable of developing new products through research, development and marketing, in particular focusing on cancer therapy. Many large pharmaceutical companies are big players in the current protein-based therapeutic market. They are interested in protein or peptide-based drugs in treating diseases other than cancers. We expect that our strength in protein delivery will get their interests and potentially lead to partnership with them. In addition to protein delivery, these novel proprietary materials and formulation are also useful for siRNA and miRNA delivery. There will be opportunities to build partnership with companies who are interested in this area. Benefits of this system compared to other common liposomal protein delivery systems include that it is applicable to any protein therapeutic, it utilizes an efficient, cost-effective methodology for cheap, scalable synthesis of lipids, it provides a traceless delivery method, and it involves small broadly-applicable nanocomplexes similar to those already used by drug companies for RNAi formulations and delivery.
How well does your solution compete against other solutions in development and on the market?
Currently there is no effective solution in delivering therapeutic proteins or peptides intracellularly. Many are in the investigation stage, but no commercial products are on the market yet.
Describe your company funding status.
Academic grants
Describe the key milestones for the opportunity and the challenges and risks associated with meeting these milestones.
Delivery formulations for several protein-based therapeutics were optimized, and nanocomplexes were visualized by microscopy. Cellular uptake of proteins was confirmed by FACS and fluorescence imagery for multiple protein/lipid complexes. In vitro toxicity data in 8 separate cancer cell lines shows these drug formulations exhibit EC 50 values in the low nM range (1 ‐ 250 nM depending on the cancer cell line and protein drug combination) and that the lipid nanoparticle formulation alone elicits negligible toxicity. Initial in vivo experiments have proved efficacious in a mouse cancer model. Next steps involve PK/PD and bioavailability studies for promising protein formulations.
What are your immediate needs that can be addressed by the BiotechTuesday community?
Funding, Corporate partnerships