Sci Trans Med: A breakthrough in gene therapy.

11, 2020 /----- In a recent study, scientists from the Children's Medical Research Institute found strategies that could help improve the treatment of severe liver genetic diseases.
paper was published in the journal Science Translational Medicine.
-related virus 2 (AAV2) is a viral vector that acts as a carrier for carrying therapeutic DNA to target cells in the body in specific gene therapies.
it is achieved by binding a "subject" to the target cell, which tells the carrier it is in the right place and helps transport its cargo to the cell.
, however, the success rate of clinical trials using the vector for liver disease is surprisingly low, and now CMRI researchers seem to have found the reason.
Leszek Lisowski, head of the research team at www.pixabay.com, and Professor Ian Alexander, head of the gene therapy research team, found that the original AAV2, commonly used in preclinical and clinical studies, was associated with its subject, sulphuric acid. The acetylheparin protein polysaccharide (HSPG) binds tightly, but it is not a good thing: since HSPGs are present in many parts of the body, not just in liver cells, the vector is "captured" before reaching its intended destination.
, few carriers managed to deliver their therapeutic drugs to the liver, which greatly reduced the effectiveness of treatment.
led the CMRI team to study the naturally occurring adeno-related virus, which they found was more successful in getting the therapy into the liver.
viruses use another as-yet-unsealed subject.
CMRI researchers are now able to use this better subject in the lab instead of HSPGs to prepare vectors, potentially making next-generation gene therapy for the liver more successful.
"This does challenge a fundamental concept in our field, namely that strong binding to HSPG is essential for AAV to enter human cells, and suggests that vectors of other receptors used by natural AAVs targeting the origin of human liver may be more effective for clinical genes," said Dr Laskowski.
our findings will shake the foundation of AAV-based gene therapy.
added: "This provides us with new ideas, challenges our previous understanding, and corrects misconceptions about how vectors bind to cells."
lead author Dr Marti Cabanes-Creus said they could now continue to improve the use of vectors to help children with liver disease.
will help us understand previous clinical data and how to improve it," he said.
by using better carriers, we can improve safety and efficiency.
the cost of these treatments will be reduced because lower doses are needed to achieve therapeutic results.
.com Source: Discovery Challenges the Foundations of gene therapy Source: M. Cabanes-Creus el al., "Restoring the natural tropism of AAV2 vectors for human liver," Science Translational Medicine (2020). stm.sciencemag.org/lookup/doi/ ... scitranslmed.aba3312.