Granted Patent
B2
US 12,465,657 · App. 17/816,139 · Granted Nov 11, 2025
Enhanced delivery of viral particles to the striatum and cortex
Assignee:
Genzyme Corporation
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Abstract
Provided herein are novel methods for delivering recombinant adeno-associated viral (rAAV) particles to the central nervous system of a mammal (e.g., a human). In aspects, the methods involve administering rAAV particles containing a heterologous nucleic acid to the striatum and causing expression of the heterologous nucleic acid in at least the cerebral cortex and the striatum of the mammal.
Claims (10)
1 . A method for delivering a recombinant adeno-associated viral (rAAV) particle comprising an AAV serotype 2 (AAV2) capsid to the central nervous system of a mammal comprising using a convection enhanced delivery system comprising a cannula to deliver a composition comprising the rAAV particle to the putamen of each hemisphere of the striatum at a rate from about 3 uL/min to about 5 μL/min, wherein the rAAV particle comprises an rAAV vector comprising a heterologous nucleic acid encoding amino acid decarboxylase and the rAAV vector is operably linked to a cytomegalovirus immediate early promoter, wherein the rAAV particle undergoes retrograde transport in the cerebral cortex, and wherein the heterologous nucleic acid is expressed in either the prefrontal association cortical areas and the extensive regions of the occipital cortex of the brain of the mammal.
2 . The method of claim 1 , wherein the viral titer of the rAAV particles is from 5×10 10 to 100×10 10 infectious units/mL.
3 . The method of claim 1 , wherein the viral titer of the rAAV particles is from 5×10 10 to 10×10 10 infectious units/mL.
4 . The method of claim 1 , wherein the viral titer of the rAAV particles is from 50×10 10 to 100×10 10 infectious units/mL.
5 . The method of claim 1 , wherein the viral titer of the rAAV particles is from 10×10 10 to 50×10 10 infectious units/mL.
6 . The method of claim 1 , wherein the viral titer of the rAAV particles is from 5×10 9 to 100×10 9 transducing units/mL.
7 . The method of claim 1 , wherein the viral titer of the rAAV particles is from 50×10 9 to 100×10 9 transducing units/mL.
8 . The method of claim 1 , wherein the viral titer of the rAAV particles is from 25×10 9 to 50×10 9 transducing units/ml.
9 . The method of claim 1 , wherein the viral titer of the rAAV particles is from 5×10 9 to 25×10 9 transducing units/mL.
10 . The method of claim 1 , wherein positioning of the cannula is monitored by MRI.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 1, 2022
From: STANEK, LISA M; SHIHABUDDIN, LAMYA
To: GENZYME CORPORATION
Reel/Frame 060971/0175 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 1, 2022
From: STANEK, LISA M.; SHIHABUDDIN, LAMYA
To: GENZYME CORPORATION
Reel/Frame 060971/0179 →
Continuity (4)
Continuation
15549962
Provisional Application
62114544
· Feb 10, 2015
Provisional Application
62220997
· Sep 19, 2015
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