At the forefront of personalized medicine, cell and gene therapy are areas of biomedical research that aim to treat the underlying cause of both genetic and acquired diseases.
Advancements in the field of human genomics, transcriptomics, and proteomics have given rise to high-throughput, affordable, and potentially life-changing cell and gene therapies to treat individuals with genetic diseases. Cell therapy works by introducing healthy cells into a patient's body to replace or repair damaged cells, and gene therapy works by introducing genetic material to target cells via a vector to modify the expression of a gene. Cell and gene therapies can be combined and typically offer longer-lasting effects than traditional medicines. As our understanding of the human genome continues to improve, more sophisticated gene-editing tools become available, promising a new era of personalized medicine.
In this resource, we explore the different approaches available for safe and effective delivery of cell and gene therapies into target cells.
Nucleic acids, DNA and RNA, are essential to all known forms of life, playing a primary role in the storage and expression of genomic information.
Recent developments in human genomics, transcriptomics, and proteomics have led to the advancement of nucleic acid-based therapeutics. With an increasing number of nucleic acid therapeutics now available, gene-based therapies are promising a new era of genetic medicine.
There are a number of different approaches to nucleic acid-based therapeutics, which can provide long-lasting and effective effects via gene editing, insertion, replacement, or inhibition. These specific approaches require the delivery of a nucleic acid sequence into target cells, and there are several delivery approaches available, such as conjugation with lipid nanoparticles (LNPs) or encapsidating in viral vectors for effective targeted delivery. The effectiveness of their translation, however, depends on the delivery tools and technologies.
Lipid-mediated delivery systems have been developed to facilitate the transfer of large macromolecules such as nucleic acids across the plasma membrane.
LNPs provide a protected mode of transport for nucleic acids, as their size, lipid composition, charge, and surface chemistry allow them to cross the plasma membrane and eliminate the risk of nuclease degradation and endosomal digestion, enabling nucleic acids to enter the cell. The delivery approach can be optimized for different types of nucleic acid and the selection of specific lipid characteristics enables targeted delivery to certain cell types or tissues.
Each component that makes up the LNP delivery system must be meticulously analyzed and controlled as it has been shown that impurities can lead to mRNA degradation and lower potency. It is therefore imperative to implement impurities screening to ensure drug safety and efficacy.
Download the free resources below to find out more about rapid LNP analysis:
Another approach to delivering nucleic acid sequences into cells is by encapsidating them in viral vectors.
Modified viruses are used as a vehicle to deliver nucleic acid across the nuclear membrane and into cells due to their natural ability to infect cells and release their genetic payload. Once the genetic information is released into the host cell, the gene product is expressed.
Viral vector delivery systems offer advantages such as long-term gene expression, however, to ensure safety and efficacy, careful monitoring of critical quality attributes across development, manufacturing, and QC is crucial. Analytical methods such as anion exchange (AEX) chromatography, post-translational modification (PTM) analyses, reversed-phase (RP) chromatography, and size exclusion chromatography (SEC) are just some of the methods available to monitor the nucleic acid-based therapeutic.
Explore our free resources on the analysis of adeno-associated virus (AAV) preparations:
Due to the complex nature of cell and gene therapies, managing residual impurities in downstream processing is a challenging yet critical step to ensure the safety and efficacy of these biotherapeutics.
From LC-optical workflows to support LNP development to pipetting instruments and chromatography columns, Waters offers a comprehensive portfolio of compliance-ready LC-MS solutions to support cell and gene therapy development. Find out more about Waters key products designed to eliminate doubt in your LC-MS workflows:
Watch the video below to discover how Waters strives to provide you with the confidence that your method is consistent and reproducible, batch-to-batch, year-to-year.
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