Compositions and methods for treating amyotrophic lateral sclerosis
AssigneeVoyager Therapeutics, Inc.
InventorsMathieu Emmanuel Nonnenmacher, Tyler Christopher Moyer, Jiangyu Li, Dan Richard Laks, Cansu Colpan, Michael D. Grannan
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Abstract
The present disclosure relates to AAVs encoding a SOD1 targeting polynucleotide which may be used to treat amyotrophic lateral sclerosis (ALS) and delivery methods for the treatment of spinal cord related disorders including ALS.
Claims62
An AAV particle comprising an AAV capsid variant and a nucleic acid encoding a polynucleotide that targets human SOD1, wherein the AAV capsid variant comprises an amino acid sequence having the following formula:
- [N1]-[N2]-[N3], wherein:
- (i) [N1] comprises X1, X2, and X3, wherein at least one of X1, X2, or X3 is G;
- (ii) [N2] comprises the amino acid sequence of SPH;
- and
- (iii) [N3] comprises X4, X5, and X6, wherein at least one of X4, X5, or X6 is a basic amino acid, e.g., a K or R;
- wherein [N1]-[N2]-[N3] is present in hypervariable loop IV;
- and
- wherein the AAV capsid variant comprises an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO:
- 138.
An AAV particle comprising an AAV capsid variant and a nucleic acid encoding a polynucleotide that targets human SOD1, wherein the AAV capsid variant comprises:
- (i) the amino acid sequence of SPHSKA (SEQ ID NO:
- 941) in hypervariable loop IV;
- and
- (ii) an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO:
- 138.
An AAV particle comprising an AAV capsid variant and a nucleic acid encoding a polynucleotide that targets human SOD1, wherein the AAV capsid variant comprises:
- (i) the amino acid sequence of HDSPHK (SEQ ID NO:
- 2) in hypervariable loop IV;
- and
- (ii) an amino acid sequence at least 95% identical to the amino acid sequence of positions 203-736 of SEQ ID NO:
- 138.
An AAV particle comprising:
- (i) an AAV capsid variant comprising the amino acid sequence of SEQ ID NO:
- 69;
- and
- (ii) a nucleic acid encoding a polynucleotide targeting human SOD1, wherein the encoded polynucleotide comprises a siRNA comprising a sense strand sequence and an antisense strand sequence, wherein the encoded sense strand sequence comprises SEQ ID NO:
- 2525, and the encoded antisense strand sequence comprises SEQ ID NO:
- 2507.
An AAV particle comprising:
- (i) an AAV capsid variant comprising the amino acid sequence of SEQ ID NO:
- 36;
- and
- (ii) a nucleic acid encoding a polynucleotide targeting human SOD1, wherein the encoded polynucleotide comprises a siRNA comprising a sense strand sequence and an antisense strand sequence, wherein the encoded sense strand sequence comprises SEQ ID NO:
- 2525, and the encoded antisense strand sequence comprises SEQ ID NO:
- 2507.
An AAV particle comprising:
- (i) an AAV capsid variant comprising the amino acid sequence of SEQ ID NO:
- 982;
- and
- (ii) a nucleic acid encoding a polynucleotide targeting human SOD1, wherein the encoded polynucleotide comprises a siRNA comprising a sense strand sequence and an antisense strand sequence, wherein the encoded sense strand sequence comprises SEQ ID NO:
- 2525, and the encoded antisense strand sequence comprises SEQ ID NO:
- 2507.
An AAV particle comprising:
- (i) an AAV capsid variant comprising the amino acid sequence of SEQ ID NO:
- 69;
- and
- (ii) a nucleic acid encoding a polynucleotide targeting human SOD1, wherein the encoded polynucleotide comprises the nucleotide sequence of SEQ ID NO:
- 5013.
An AAV particle comprising:
- (i) an AAV capsid variant comprising the amino acid sequence of SEQ ID NO:
- 36;
- and
- (ii) a nucleic acid encoding a polynucleotide targeting human SOD1, wherein the encoded polynucleotide comprises the nucleotide sequence of SEQ ID NO:
- 5013.
An AAV particle comprising:
- (i) an AAV capsid variant comprising the amino acid sequence of SEQ ID NO:
- 982;
- and
- (ii) a nucleic acid encoding a polynucleotide targeting human SOD1, wherein the encoded polynucleotide comprises the nucleotide sequence of SEQ ID NO:
- 5013.
An AAV particle comprising:
- (i) an AAV capsid variant comprising the amino acid sequence of SEQ ID NO:
- 69;
- and
- (ii) a viral genome comprising the nucleotide sequence of SEQ ID NO:
- 109.
An AAV particle comprising:
- (i) an AAV capsid variant comprising the amino acid sequence of SEQ ID NO:
- 36;
- and
- (ii) a viral genome comprising the nucleotide sequence of SEQ ID NO:
- 109.
An AAV particle comprising:
- (i) an AAV capsid variant comprising the amino acid sequence of SEQ ID NO:
- 982;
- and
- (ii) a viral genome comprising the nucleotide sequence of SEQ ID NO:
- 109.
Dependencies are inferred from the claim text.