CASIS PCG 3 (CASIS PCG 3) - 10.11.17

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
To fight multiple diseases and pathogens, the human immune system produces a wide range of cells and proteins, including proteins called monoclonal antibodies. Crystallizing these proteins allows pharmaceutical researchers to study them in detail, and crystallizing them in microgravity produces larger, more perfect specimens. The Center for the Advancement of Science in Space - Protein Crystal Growth-3 (CASIS PCG-3) investigation crystallizes human monoclonal antibodies developed by Merck Research Labs, which are undergoing clinical trials for the treatment of several diseases.
Science Results for Everyone
Information Pending

The following content was provided by Paul Reichert, M.S., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: PCG-3

Principal Investigator(s)
Paul Reichert, M.S., Merck Research Laboratories, Kenilworth, NJ, United States

Co-Investigator(s)/Collaborator(s)
Information Pending

Developer(s)
Information Pending

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Earth Benefits

ISS Expedition Duration
March 2015 - September 2015

Expeditions Assigned
43/44

Previous Missions
Numerous protein crystal growth investigations have been completed on ISS. The CASIS PCG-3 Principal Investigator (PI) has been the PI on 12 previous Space Shuttle flights and two ISS flights (most recently increment 39/40). These experiments were designed to explore microgravity effects on multiple pharmaceutical applications primarily using alpha interferon (Intron A™). These applications included structure determination, drug delivery and the purification of protein therapeutics. Space grown crystalline suspensions of alpha interferon from STS-70, because of their high quality and uniformity compared to earth grown crystals, were used in multiple primate pharmacological studies.

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Experiment Description

Research Overview

  • The CASIS PCG-3 investigation focuses on the crystallization of human monoclonal antibodies developed by Merck Research Labs.
  • High quality crystals can be used by the pharmaceutical industry to determine protein structure, improve drug delivery and drug purification methods and to develop better methods for the storage of biologically active ingredients.

Description

Growth of crystals that diffract to higher resolution could be the difference between getting interpretable and un-interpretable data, leading to a high resolution structure. Structural information could help in the understanding of the functional parts of monoclonal antibodies such as epitope binding and help envision the design of new and improved monoclonal antibodies.
 
The CASIS PCG-3 project uses few resources and has a flexible strategy that makes it an ideal system for ISS. The CASIS PCG-3 hardware launches in a Double Cold Bag at +4°C to prevent crystal formation prior to reaching microgravity. The experiment samples in the Handheld HDPCG hardware are activated by turning the sample cells 90 degrees clockwise to introduce the sample insert to the precipitant reservoir. Following the Handheld HDPCG activation, the hardware assemblies are transferred to the Microgravity Experiment Research Locker/Incubator (MERLIN). The temperature in MERLIN is set at +30°C. Following approximately 18 days of crystal growth, the assemblies are removed from MERLIN. The Handheld HDPCG experiment samples are deactivated by turning the sample cells 180 degrees clockwise. This operation turns the protein insert opposite of the precipitant reservoir and stops the experiment. The HDPCG assemblies return at ambient temperature in a soft stowage bag. The PCG Vials return at +4C in passive cold stowage.

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Applications

Space Applications
Crystals consist of repeating patterns of molecules organized in three dimensions, enabling researchers to see a molecule’s structure in much finer detail. Microgravity provides an ideal environment to grow large, complex crystals because gravity and convection do not interfere with their formation. The International Space Station is an ideal laboratory for protein crystallization research, which involves building large, high-quality crystals of complex proteins for use in biomedical studies. The investigation builds on previous data gained from earlier spaceflight experiments, furthering the use of the ISS as a scientific laboratory.

Earth Applications
Protein crystallization helps researchers study how proteins work, and to design new formulations that can improve patient health. Crystallization technology enables the design of proteins for high-dose uses, changes the way drugs are administered, from intravenous tubes to injections, and designs proteins that take longer to break down. The monoclonal antibodies used in this investigation are undergoing clinical trials for treating various human diseases, benefiting people on Earth.

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Operations

Operational Requirements and Protocols

The time between turnover and launch is launch minus 24 hours. While on-orbit, the specimen require refrigerated stowage prior to being transferred to a MERLIN. Sample activation must be completed within 6 days following the vehicle launch. The sample removal and deactivation can occur as soon as 18 days after the MERLIN installation. Ambient stowage is sufficient for the return flight. Temperatures must be maintained above 10°C. Early recovery at the dock is required and samples will be shipped to the appropriate laboratory for X-ray crystallography.

The Handheld HDPCG assemblies are transferred from cold stowage on the ascent vehicle to ISS. To activate the experiment samples in the Handheld HDPCG hardware, an Activation Tool (which is attached to the side of the HDPCG hardware using Velcro) is removed and attached to each of the five cell blocks. Each cell block is turned 90 degrees clockwise to align the sample insert with the precipitant solution. Following Handheld HDPCG activation, the hardware assemblies are transferred to MERLIN. MERLIN provides +30°C for the experiment samples. Crystals grow in MERLIN for approximately 18 days and then the hardware assemblies are removed from MERLIN. The Handheld HDPCG experiment samples are deactivated by attaching the Activation Tool to each cell block and turning 180 degrees clockwise to turn the protein insert opposite of the precipitant reservoir. Prior to unberth, the HDPCG hardware assemblies are transferred to ambient stowage on the descent vehicle for return. The PCG Vials remain at +4C on ISS and during return.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Information Pending

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Related Websites

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Imagery