Biodistribution testing of cell and gene therapies

Cell and gene therapy drug products represent a rapidly growing field in the development of new treatments for a wide range of diseases. These therapies have the potential to revolutionize medicine by offering cures rather than just managing symptoms. However, with this potential comes unique challenges, particularly with regard to biodistribution testing.

Biodistribution testing is the study of where a drug product goes in the body after administration. In the case of cell and gene therapy, this is particularly important because these products are often designed to target specific tissues or organs. Biodistribution testing can help determine if the therapy is reaching its intended target, if it is being distributed evenly throughout the body, and if it is accumulating in unintended locations.

One of the key reasons biodistribution testing is so important for cell and gene therapy is because of the potential for off-target effects. These therapies are often highly targeted, meaning that they are designed to affect only specific cells or tissues. However, if the therapy is not distributed as intended, it could potentially affect other parts of the body, causing unintended side effects.

Another important reason for biodistribution testing is important to assess the safety of the therapy. In some cases, a therapy may be safe in one part of the body but could cause harm if it accumulates in another. For example, a gene therapy that targets the liver may be safe if it stays in the liver, but could cause liver damage if it spreads to other organs.

Last, biodistribution testing is important for understanding the efficacy of a therapy. If a therapy is not reaching its intended target, it may not be effective in treating the disease it was designed for. By understanding how the therapy is distributed throughout the body, researchers can adjust the therapy to improve its efficacy.

Biodistribution studies typically involve several steps:

1. Animal model selection: Biodistribution studies are often conducted in animal models, such as mice, rats, or non-human primates. The choice of animal model depends on the specific research question, the characteristics of the substance being studied, and ethical considerations.
2. Administration of the substance: The substance being studied is administered to the animal model, either through injection, oral ingestion, or inhalation. The dose and timing of administration are carefully controlled to ensure consistent results.
3. Tissue collection: After administration of the substance, tissue samples are collected from various organs and tissues throughout the body, such as the liver, spleen, lungs, and brain. The timing and frequency of tissue collection depends on the specific research question and the pharmacokinetics of the substance being studied.
4. Sample preparation: The tissue samples are prepared for analysis, which may involve homogenization, sectioning, or staining, depending on the analysis method being used.
5. Analysis of tissue samples: The tissue samples are analyzed using one or more of the methods described earlier, such as droplet digital PCR (ddPCR), quantitative polymerase chain reaction (qPCR), or next-gen sequencing (NGS). The data generated from these analyses are used to quantify the amount of the substance in each tissue and to visualize the distribution of the substance throughout the body.
6. Data interpretation: The data generated from the biodistribution study are analyzed and interpreted to understand how the substance is distributed throughout the body and which organs or tissues are affected. This information is used to guide further research and to inform clinical development of the substance.

Overall, biodistribution testing is a critical component of the development of cell and gene therapy drug products. By understanding how the therapy is distributed throughout the body, researchers can ensure its safety and efficacy, and improve its overall success as a treatment for a wide range of diseases. However, biodistribution studies are complex experiments that require careful planning and execution to ensure accurate and reproducible results. The methods and techniques used may vary depending on the specific research question and the characteristics of the substance being studied.

Avance offers several assays for biodistribution studies for gene and cell therapies:

Biodistribution of DNA Viral Vectors or Transgenes

The biodistribution of viral vectors or transgenes is an important part of pre-clinical pharmacokinetics and toxicity studies. To support biodistribution studies, Avance offers GLP and Non-GLP qPCR, ddPCR, and NGS testing services. Our team has extensive experience in qPCR biodistribution assay development, validation, and sample testing.

Biodistribution of RNA Transgenes

The biodistribution of RNA transgenes is typically a requirement for RNA-based CGT products. To determine RNA transgene biodistribution, we provide RT-qPCR method with RNA standard curves to test genes that are not naturally present in testing animals.

Biodistribution of Therapeutic Cells

Determining the biodistribution of therapeutic cells is essential for understanding the efficacy and safety of a cell and gene therapy product. The team at Avance Biosciences™ has much expertise in developing sensitive and specific qPCR, ddPCR, and NGS methods to quantify human cells in animal tissues.

Single-cell Biodistribution Studies

Assessing the biodistribution of both ex vivo and in vivo cell and gene therapies is critical for ascertaining drug efficacy and safety prior and during clinical studies. Tapestri’s® multi-attribute, multi-omic single-cell platform can be used to accurately detect cell therapy distribution throughout the body, as well as detection of modified target cells from in vivo gene therapies in a variety of tissue types.

Whether you are working on plasmid-based or AAV gene therapies, CAR-T cell therapeutics, or iPSC-based therapies, Avance Biosciences™’ experienced team of scientists has seen it all. We can assist you in developing specific and sensitive assays for your biodistribution studies.