New gene delivery vehicle shows promise for human brain gene therapy

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"In an important step toward more effective gene therapies for brain diseases, researchers ... have engineered a gene-delivery vehicle that uses a human protein to efficiently cross the blood-brain barrier and deliver a disease-relevant gene to the brain in mice expressing the human protein. Because the vehicle binds to a well-studied protein in the blood-brain barrier, the scientists say it has a good chance at working in patients.
Gene therapy could potentially treat a range of severe genetic brain disorders, which currently have no cures and few treatment options. But FDA-approved forms of the most commonly used vehicle for packaging and delivering these therapies to target cells, adeno-associated viruses (AAVs), aren’t able to efficiently cross the blood-brain barrier at high levels and deliver therapeutic cargo. ..."

From the abstract:

"Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an adeno-associated virus (AAV) capsid, BI-hTFR1, that binds human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier (BBB). BI-hTFR1 was actively transported across human brain endothelial cells and, relative to AAV9, provided 40–50 times greater reporter expression in the CNS of human TFRC knock-in mice. The enhanced tropism was CNS-specific and absent in wild type mice. When used to deliver GBA1, mutations of which cause Gaucher disease and are linked to Parkinson’s disease, BI-hTFR1 substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared to AAV9. These findings establish BI-hTFR1 as a potential vector for human CNS gene therapy."

New gene delivery vehicle shows promise for human brain gene therapy | Broad Institute Scientists have engineered an adeno-associated virus (AAV) that efficiently crosses the blood-brain barrier in human cell models and delivers genes throughout the brain in humanized mice.

An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery (no public access)

Brain vasculature (in blue) surrounded by RNA (in orange) transcribed from the gene delivered to the brain in humanized mice using an engineered AAV targeting the human transferrin receptor.