Highly effective biotherapeutics, such as monoclonal antibodies (MAb), proteins and nucleic acids, are unable to enter the cell and reach their cellular target. This leaves a vast number of potential therapeutic targets untapped, many of which are “undruggable” by conventional methods. There is an overwhelming need for systematic cell-targeting systems that deliver bioactive cargo to a specific cell type and to precise locations within that cell. To overcome this problem, we have advanced a platform technology, referred to as FOX Three™, which has unprecedented capability to rapidly identify peptidic molecular guidance systems (MGSs). Identified MGSs home onto desired cell types and deliver payloads to discrete subcellular locations within those cells. This provides a level of cellular targeting that is not available with current technologies.
FOX Three utilizes highly diverse, phage-displayed peptide libraries to rapidly identify MGSs. Peptides are a well-understood class of biomolecule that are easily synthesized by biological or chemical processes. As a result, the power of the FOX Three platform is demonstrated in its speed and flexibility. It can be applied to any cell type, regardless of our knowledge about the molecular features of that cell, producing lead MGSs in 4-6 weeks. Selected MGSs are readily engineered for optimal performance. Furthermore, we have demonstrated that MGSs can deliver virtually any cargo inside the target cells, regardless of size or composition.
We have identified greater than 40 MGSs that target differing cell types ranging from cancer to cardiomyocytes. Chemical optimization results in MGSs with affinities ranging from 1-40 nM for their cellular target, serum stability of >48 hours and 50-1000-fold specificity for their target cells compared to control cells. The rate of MGS internalization is rapid with t1/2 of internalization between 10-30 minutes, driving uptake against a concentration gradient. As a result, MGSs reach intracellular concentrations up to 1.5 µM.
We have identified MGSs that traffic to five different subcellular locations and demonstrated the importance of subcellular delivery for biological efficacy. MGSs are amenable to a range of conjugation chemistries and attachment of therapeutic cargo does not significantly impact the MGS’s affinity, cell specificity or ability to internalize. MGSs home to their target cell type in vivo and redirect biotherapeutics to the desired tissues.
Register for this webinar to hear the FOX Three platform presented, focusing on our approach to identify, optimize and characterize MGSs. Examples of MGS conjugates for guided delivery of nucleic acids (ASO and siRNA) and proteins (Mab and Toxins) will be discussed.
Kathlynn Brown, Senior Director, Macromolecular Biosciences, SRI International
Kathlynn Brown, PhD, is the Senior Director of Macromolecular Biosciences at SRI International. Her laboratory was among the first to adopt cell-based biopanning of phage-displayed peptide libraries. Using this approach, her team developed a suite of high affinity peptides that target a variety of cell types ranging from cancer to cardiomyocytes. They advanced the platform to identify delivery systems that exhibit both cellular and subcellular specificity, allowing for precision delivery previously unobtainable. These peptides deliver numerous cargos, opening new avenues for intracellular transport of biotherapeutics. Recently, her lab adapted the platform to identify peptides capable of delivery to the central nervous system.
Dr. Brown obtained her PhD in organic chemistry at the University of Texas at Austin. She continued training at UCSF as a Damon Runyon Walter Winchell Postdoctoral Fellow. Before moving to SRI in 2014, she was on the faculty at the University of Texas Southwestern Medical Center.
Who Should Attend?
Biopharmaceutical researchers developing immunotherapeutics for solid tumors, with relevant job titles including:
- Directors, Biotherapeutics
- Research & Development Managers/Directors for Cancer Immunotherapy
- Research & Development Scientists
- Research Oncologists
- Pharmaceutical Program Development and Management
- Translational Researchers
- Pharmaceutical Business Development
What You Will Learn
In this webinar, participants will learn:
- Molecular Guidance Systems, or MGSs, can be rapidly identified for virtually any cell type
- MGS’s can deliver a wide variety of cargoes, ranging from small molecules to full length antibodies
- MGS’s can achieve cell specific and subcellular specific delivery
- MGS’s conjugates can reach high intracellular concentrations in the target cell resulting in biological efficacy
SRI International, a non-profit research institute founded in 1946 and headquartered in Menlo Park, California, creates world-changing solutions to make people safer, healthier, and more productive. SRI Biosciences, a division of SRI International, integrates basic biomedical research with drug and diagnostics discovery, and preclinical and clinical development. SRI Biosciences has advanced more than 175 drugs to clinical trials, and approximately 20 have reached the market. The division is focused on novel platforms and programs in a variety of therapeutic areas targeting Discovery through Preclinical development in high unmet medical need areas. SRI Biosciences collaborates with a broad range of partners from small and virtual biotechnology companies to top pharmaceutical companies and other leading industry partners. More information is available at www.sri.com/biosciences.
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