Methods and systems for noninvasive control of brain cells and related vectors and compositions

A method to control a target brain cell activity with respect to a target neural circuit of an individual, the method comprising

• (i) applying focused ultrasound to a target brain region of the individual at a mechanical index of 0.2 to 0.6 the target brain region comprising the target brain cell, and
• (ii) systemically administering to the individual an effective amount of microbubble contrast agents, 1.2E7 to 1.21E10 per kg of the individual;
• wherein the applying focused ultrasound and the systematically administering microbubble contrast agent is performed to induce transient blood-brain barrier opening at the target brain region;
• the method further comprising
• (iii) systemically administering to the individual an effective amount of at least 1E9 per kg of the individual of an expression vector configured to enter the brain at the transient blood-brain barrier opening and to specifically deliver and express in the target brain cell a gene encoding a chemogenetic protein under control of a cell-type specific promoter configured to be cell-type specifically active in the target brain cell,
• wherein
• the chemogenetic protein is configured to activate or inhibit the target brain cell activity following binding with a corresponding chemical actuator or metabolite thereof,
• the applying, the systemically administering an effective amount of microbubble contrast agents, and the systemically administering an effective amount of an expression vector, are performed in combination to specifically deliver and cell-type specifically express the gene encoding a chemogenetic protein in a controlled percentage population of at least 20% of the target brain cells in the target brain region to obtain a chemogenetically treated target brain region in which the target brain cells of the controlled percentage population comprise the chemogenetic protein;
• and
• the systemically administering of an expression vector is performed in combination with the applying focused ultrasound, and the systematically administering microbubble contrast agent to have vectors carrying genetic material in blood concurrently with the occurrence of the transient blood-brain barrier opening;
• the method further comprising
• (iv) systemically administering to the individual the corresponding chemical actuator, to allow binding of the corresponding chemical actuator or a metabolite thereof with the chemogenetic protein in the target brain cells of the controlled population of the chemogenetically treated target brain region, and activation or inhibition of the target brain cell activity.