Intrathecal delivery of recombinant Adeno-associated virus 9
The present invention relates to Adeno-associated virus type 9 methods and materials useful for intrathecal delivery of polynucleotides. Use of the methods and materials is indicated, for example, for treatment of lower motor neuron diseases such as SMA and ALS as well as Pompe disease and lysosomal storage disorders. It is disclosed that administration of a non-ionic, low-osmolar contrast agent, together with a rAA9 vector for the expression of Survival Motor Neuron protein, improves the survival of SMN mutant mice as compared to the administration of the expression vector alone.
1. A method of delivering a polynucleotide to the central nervous system (CNS) of a patient in need thereof, comprising delivering intrathecally to the patient a composition comprising (i) a recombinant AAV9 (rAAV9) genome for treating mucopolysaccharidosis (MPS I), wherein the genome comprises the polynucleotide, and (ii) non-ionic, low-osmolar contrast agent, wherein intrathecal administration of the rAAV9 genome delivers the polynucleotide to the CNS of the patient.
2. The method of claim 1 , wherein the polynucleotide is delivered to the brain.
3. The method of claim 1 , wherein the polynucleotide is delivered to the spinal cord.
4. The method of claim 1 , wherein the polynucleotide is delivered to a glial cell.
5. The method of claim 4 , wherein the glial cell is an astrocyte.
6. The method of claim 1 , wherein the polynucleotide is delivered to a neuron.
7. The method of claim 1 , wherein the non-ionic, low-osmolar contrast agent is iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, or a combination thereof.
8. The method of claim 1 , wherein the non-ionic, low-osmolar contrast agent is iohexol.
9. The method of claim 1 , wherein the rAAV9 genome is a self-complementary genome.
10. The method of claim 1 , wherein the rAAV9 genome is a single-stranded genome.
11. The method of claim 1 , wherein the patient is suffering from MPS I.
12. The method of claim 1 , wherein the composition is formed by mixing the rAAV9 genome with the contrast agent prior to delivering intrathecally to the patient.
13. The method of claim 1 , wherein the rAAV9 genome and the contrast agent are delivered sequentially.