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Written byWang CongEditor
Wang Duoyu TypesettingShui Chengwen
Researchers have been trying different ways to deliver genes to the brain to treat central nervous system diseases such as brain tumors and neurodegenerative diseases
.
But because of the blood-brain barrier (BBB), delivering genes to the brain becomes a challenge
.
Recently, the team of Associate Professor Chen Hong of Washington University in St.
Louis published a paper in the journal eBioMedicine titled: Incisionless targeted adeno-associated viral vector delivery to the brain by focused ultrasound-mediated intranasal administration research paper
.
The study, which validates the team's previously developed focused ultrasound intranasal delivery (FUSIN) method in a mouse model for the first time, confirms that FUSIN is able to break through the blood-brain barrier (BBB) and convert adeno-associated viral vectors (AAV) is efficiently delivered to the brain
through the nose.
This delivery efficiency works better than other delivery methods and has minimal
impact on other organs in the body.
Chen Hong's team began applying focused ultrasound intranasal delivery (FUSIN) several years ago, and in 2018 used FUSIN to deliver gold nanoparticles.
The effect
was verified in a brain tumor model in 2021.
FUSIN is administered to the brain through the nose and bypasses the blood-brain barrier, minimizing contact
with the rest of the body when the drug to be delivered.
Adeno-associated viral vectors (AAVs) are currently the main delivery vectors for gene therapy and have the potential to
deliver and treat a variety of central nervous system diseases.
There are many ways to deliver AAV to the central nervous system, such as direct intracranial injection (DI), intranasal delivery (IN), intravenous injection combined with focused ultrasound to induce blood-brain barrier disruption (FUS-BBBD).
However, how to deliver AAV to the brain with minimal systemic toxicity, non-invasive and efficient remains a major challenge
.
In this study, the research team explored the effects of
using FUSIN to deliver adeno-associated virus to the brain through the nose.
The team found that adeno-associated virus type 5 (AAV5-hSyn-EGFP), which carries green fluorescent protein (GFP), is passed through focused ultrasound Ultrasound) and microbubbles deliver GFP to the cerebral cortex and brainstem, and because GFP is initiated by the neuron-specific promoter hSyn, it is not expressed
in other tissues and organs.
The experimental results showed that the delivery efficiency of FUSIN was similar to that of direct intracranial injection (DI), which was more than 400 times higher than intravenous injection combined with focused ultrasound to induce blood-brain barrier disruption (FUS-BBBD), and was more than intranasal delivery (IN) is more than 2000 times
higher.
In addition, FUSIN has the least impact on other organs of the body, found in small amounts in the lungs and little or no
in other organs.
Chen Hong said that focused ultrasound uses ultrasound that can penetrate the scalp and skull, targeting almost any location within the brain, where it causes periodic compression and expansion of microvesicles, acting on the walls of blood vessels.
Break through the blood-brain barrier
.
FUSIN is completely non-invasive and can successfully deliver multiple types of drugs to different brain regions
with high efficiency and minimal systemic exposure.
So far, no gene therapies have been approved for the treatment of
central nervous system disorders.
This non-invasive delivery and spatially targeted delivery of AAV to the brain by FUSIN will have significant therapeutic effects
.
Chen Hong's
research team also said that FUSIN-mediated AAV delivery may have better effects than other delivery methods, which is expected to be used to treat a variety of brain diseases, such as Parkinson's disease
。
Link: https://doi.
org/10.
1016/j.
ebiom.
2022.
104277
open for reprinting Welcome to forward to Moments and WeChat groups
Wang Duoyu TypesettingShui Chengwen
Researchers have been trying different ways to deliver genes to the brain to treat central nervous system diseases such as brain tumors and neurodegenerative diseases
.
But because of the blood-brain barrier (BBB), delivering genes to the brain becomes a challenge
.
Recently, the team of Associate Professor Chen Hong of Washington University in St.
Louis published a paper in the journal eBioMedicine titled: Incisionless targeted adeno-associated viral vector delivery to the brain by focused ultrasound-mediated intranasal administration research paper
.
The study, which validates the team's previously developed focused ultrasound intranasal delivery (FUSIN) method in a mouse model for the first time, confirms that FUSIN is able to break through the blood-brain barrier (BBB) and convert adeno-associated viral vectors (AAV) is efficiently delivered to the brain
through the nose.
This delivery efficiency works better than other delivery methods and has minimal
impact on other organs in the body.
Chen Hong's team began applying focused ultrasound intranasal delivery (FUSIN) several years ago, and in 2018 used FUSIN to deliver gold nanoparticles.
The effect
was verified in a brain tumor model in 2021.
FUSIN is administered to the brain through the nose and bypasses the blood-brain barrier, minimizing contact
with the rest of the body when the drug to be delivered.
Adeno-associated viral vectors (AAVs) are currently the main delivery vectors for gene therapy and have the potential to
deliver and treat a variety of central nervous system diseases.
There are many ways to deliver AAV to the central nervous system, such as direct intracranial injection (DI), intranasal delivery (IN), intravenous injection combined with focused ultrasound to induce blood-brain barrier disruption (FUS-BBBD).
However, how to deliver AAV to the brain with minimal systemic toxicity, non-invasive and efficient remains a major challenge
.
In this study, the research team explored the effects of
using FUSIN to deliver adeno-associated virus to the brain through the nose.
The team found that adeno-associated virus type 5 (AAV5-hSyn-EGFP), which carries green fluorescent protein (GFP), is passed through focused ultrasound Ultrasound) and microbubbles deliver GFP to the cerebral cortex and brainstem, and because GFP is initiated by the neuron-specific promoter hSyn, it is not expressed
in other tissues and organs.
The experimental results showed that the delivery efficiency of FUSIN was similar to that of direct intracranial injection (DI), which was more than 400 times higher than intravenous injection combined with focused ultrasound to induce blood-brain barrier disruption (FUS-BBBD), and was more than intranasal delivery (IN) is more than 2000 times
higher.
In addition, FUSIN has the least impact on other organs of the body, found in small amounts in the lungs and little or no
in other organs.
Chen Hong said that focused ultrasound uses ultrasound that can penetrate the scalp and skull, targeting almost any location within the brain, where it causes periodic compression and expansion of microvesicles, acting on the walls of blood vessels.
Break through the blood-brain barrier
.
FUSIN is completely non-invasive and can successfully deliver multiple types of drugs to different brain regions
with high efficiency and minimal systemic exposure.
So far, no gene therapies have been approved for the treatment of
central nervous system disorders.
This non-invasive delivery and spatially targeted delivery of AAV to the brain by FUSIN will have significant therapeutic effects
.
Chen Hong's
research team also said that FUSIN-mediated AAV delivery may have better effects than other delivery methods, which is expected to be used to treat a variety of brain diseases, such as Parkinson's disease
。
Link: https://doi.
org/10.
1016/j.
ebiom.
2022.
104277
open for reprinting Welcome to forward to Moments and WeChat groups
