Challenges in adeno-associated virus-based treatment of central nervous system diseases through systemic injection

Huang, Lan; Wan, Jie; Wu, Yunqiu; Tian, Yu; Yao, Yizheng; Yao, Shun; Ji, Xiaoyun; Wang, Shengjun; Su, Zhaoliang; Xu, Huaxi

doi:10.1016/j.lfs.2021.119142

Cited by 28 publications

(21 citation statements)

References 91 publications

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“…However, the injection dose of the new variants is still high at 2 × 10 14 vg/kg [1000]. These new variants of AAV may be only effective in the mouse, as humans lack the Ly6a receptor [1001]. Recently, the Ly6a human homologue, Ly6e, has been proposed as a novel AAV9 receptor at the human BBB [1002], although this has yet to be experimentally confirmed.…”

Section: Adeno-associated Virusmentioning

confidence: 99%

A Historical Review of Brain Drug Delivery

Pardridge

2022

Pharmaceutics

106

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The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a drug for syphilis, salvarsan, did not enter the brain, due to the presence of a blood–brain barrier (BBB). Owing to restricted transport across the BBB, FDA-approved drugs for the CNS have been generally limited to lipid-soluble small molecules. Drugs that do not cross the BBB can be re-engineered for transport on endogenous BBB carrier-mediated transport and receptor-mediated transport systems, which were identified during the 1970s–1980s. By the 1990s, a multitude of brain drug delivery technologies emerged, including trans-cranial delivery, CSF delivery, BBB disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, and biologics. The advantages and limitations of each of these brain drug delivery technologies are critically reviewed.

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Section: Adeno-associated Virusmentioning

confidence: 99%

A Historical Review of Brain Drug Delivery

Pardridge

2022

Pharmaceutics

106

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“…For example, imaging dyes and magnetic resonance imaging (MRI) are used to ensure the accuracy of the injection ( Fredericks et al, 2020 ). At the other end, a brain-wide expression can be achieved by systemic delivery (i.e., through circulation) ( Huang et al, 2021 ). Delivery into the whole brain can be enhanced by ultrasound, which can be used to temporarily break down the integrity of the blood-brain barrier and thus allow the virus to enter the brain.…”

Section: Methods Aiding Optogenetics In Neurosciencementioning

confidence: 99%

Red Light Optogenetics in Neuroscience

Lehtinen

Nokia

Takala

2022

Front. Cell. Neurosci.

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Optogenetics, a field concentrating on controlling cellular functions by means of light-activated proteins, has shown tremendous potential in neuroscience. It possesses superior spatiotemporal resolution compared to the surgical, electrical, and pharmacological methods traditionally used in studying brain function. A multitude of optogenetic tools for neuroscience have been created that, for example, enable the control of action potential generation via light-activated ion channels. Other optogenetic proteins have been used in the brain, for example, to control long-term potentiation or to ablate specific subtypes of neurons. In in vivo applications, however, the majority of optogenetic tools are operated with blue, green, or yellow light, which all have limited penetration in biological tissues compared to red light and especially infrared light. This difference is significant, especially considering the size of the rodent brain, a major research model in neuroscience. Our review will focus on the utilization of red light-operated optogenetic tools in neuroscience. We first outline the advantages of red light for in vivo studies. Then we provide a brief overview of the red light-activated optogenetic proteins and systems with a focus on new developments in the field. Finally, we will highlight different tools and applications, which further facilitate the use of red light optogenetics in neuroscience.

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“…Despite paracellular transport over a compromised BBB showing promise in animal models, the alternative method of crossing the BBB through receptor-mediated transcytosis has recently shown greater promise. These methods are divided into three categories: employing a viral vector that naturally crosses the BBB (usually, AAV9 [ 94 ]); altering vectors to attach to a particular transcellular transport receptor; and changing vectors to attach to a specific transcellular transport receptor [ 95 ]. Guided evolution was used to generate a vector that binds with an appropriate receptor despite specifying which one.…”

Section: Advances In Drug Delivery Across the Blood–brain Barriermentioning

confidence: 99%

Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier

et al. 2022

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The blood–brain barrier (BBB) has shown to be a significant obstacle to brain medication delivery. The BBB in a healthy brain is a diffusion barrier that prevents most substances from passing from the blood to the brain; only tiny molecules can pass across the BBB. The BBB is disturbed in specific pathological illnesses such as stroke, diabetes, seizures, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. The goal of this study is to offer a general overview of current brain medication delivery techniques and associated topics from the last five years. It is anticipated that this review will stimulate readers to look into new ways to deliver medications to the brain. Following an introduction of the construction and function of the BBB in both healthy and pathological conditions, this review revisits certain contested questions, such as whether nanoparticles may cross the BBB on their own and if medications are selectively delivered to the brain by deliberately targeted nanoparticles. Current non-nanoparticle options are also discussed, including drug delivery via the permeable BBB under pathological circumstances and the use of non-invasive approaches to improve brain medication absorption.

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Challenges in adeno-associated virus-based treatment of central nervous system diseases through systemic injection

Cited by 28 publications

References 91 publications

A Historical Review of Brain Drug Delivery

A Historical Review of Brain Drug Delivery

Red Light Optogenetics in Neuroscience

Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier

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