Going Beyond the Blood-Brain Barrier: Delivery of Diverse Cargo to Targeted Cells Within the Central Nervous System

Life Sciences, Pharmaceutical, Drug Discovery & Development,
  • Thursday, February 23, 2023

The blood-brain barrier is a set of specialized and highly selective cellular barriers that protects the central nervous system (CNS). While necessary under normal physiology, the blood-brain barrier prevents entry of many neurotherapeutics into the brain and biologic therapies such as antibodies and gene therapies are essentially excluded from the CNS.

SRI International has developed an unbiased screening platform to identify peptides that mediate delivery throughout the CNS without disruption of the blood-brain barrier or destruction of biological cargo. This approach, named DiaCyt (Dia: Through and Cyt: Cell), utilizes high diversity phage-displayed peptide libraries to peptides that transport cargos across a cellular barrier.


The company has identified three peptidic molecule transport systems (MTS) as lead candidates which have undergone preliminary optimization for serum stability, chemical stability and in vivo circulation time. Synthetic MTS peptides mediate transport of a protein in an in vitro model with efficiencies of eight to 20 percent. Tight junctions remain intact during peptide transport and proteinaceous cargo remains functional. Upon intravenous injection into a rat, each MTS peptide is transported into the CNS and is distributed throughout the ventricular system and within the surrounding parenchyma. Transport efficiency is enhanced three to 11-fold into the cerebrospinal fluid (CSF) and 10 to 22-fold into the brain.

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The MTS can transport proteins and monoclonal antibodies into the CNS. The identified MTSs can access the CNS but have no affinity for cells of the CNS, thus intracellular delivery of cargos to these important cell types requires additional cell-targeting agents. Towards this goal, they have also identified cell-specific peptides for microglia and neuronal cells, capable of intracellular delivery of cargos. These peptides, referred to as molecular guidance systems (MGS), display cell-specificity for their target cell type and mediate rapid uptake resulting in intracellular concentrations that range from 100 nM to 1 µM. Combining the MTS and MGS peptides allows for both transport and cell-specific targeting within the CNS.

Register today to learn more about going beyond the blood-brain barrier through the delivery of diverse cargo within the central nervous system.


Kathlynn Brown, SRI International

Kathlynn Brown, Vice President of Drug Delivery platforms, SRI International

Kathlynn Brown is Vice President of Drug Delivery platforms at SRI International. She leads an active research program at the SRI Shenandoah Valley (SV) site and oversees a team of cancer biology researchers at both SV and Menlo Park. Additionally, she serves as the Site Head for SRI’s SV labs.

She began her independent career at the University of Texas Southwestern Medical Center, and after 16 years, moved to SRI International to expand her translational research. Throughout her career, she has utilized her multidisciplinary expertise in organic chemistry, peptide chemistry, biochemistry and molecular biology to address challenges in biomedical research. Her research team is currently focusing on the development of molecularly guided systems that target cancerous tumors while avoiding normal healthy tissues. These systems can deliver proteins, DNA, drugs, nanoparticles and toxins in a cell-specific fashion. She also has an active program in the development of molecular imaging agents for diagnosis and classification of tumors.

Dr. Brown holds a bachelor’s in science degree in chemistry from Trinity University (San Antonio, TX) and a PhD in organic chemistry from the University of Texas at Austin. During her graduate school training she received fellowships from the Mahler Memorial Foundation and the Organic Division of the American Chemical Society. She continued her training at the University of California at San Francisco, where she was a Damon Runyon Walter Winchell Postdoctoral Fellow. Brown has co-authored numerous peer-reviewed papers, reviews and book chapters. Her research has been supported by NIH, DOD, the State of Texas and private foundations.

Message Presenter

Who Should Attend?

Biopharmaceutical researchers focused in neuroscience and neurodegenerative therapeutic development, with relevant job titles including:

  • Directors, Biotherapeutics
  • Research & Development Managers/Directors for Neuroscience
  • Research & Development Scientists
  • Research Neuroscientists
  • Pharmaceutical Program Development and Management
  • Translational Researchers
  • Early-stage Pharmaceutical Business Development

What You Will Learn

Attendees will learn:

  • Peptidic molecule transport systems (MTS) capable of carrying biologically active cargo into the central nervous system (CNS) can be isolated from peptide libraries
  • MTS peptides enable transport into the CNS and distribute cargo throughout the ventricular system and within the surrounding parenchyma
  • Molecular guidance system (MGS) peptides for cells of the central nervous system display cell-specificity and mediate intracellular delivery to their target cells
  • Combining the MTS and MGS peptides allows for both transport and cell-specific targeting within the CNS

Xtalks Partner

SRI International

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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