Adeno-associated virus vectors for nucleic acid delivery to retinal cells

Abstract

This document relates to AAV vectors (e.g., AAV2 vectors). For example, AAV vectors (e.g., AAV2 vectors) containing an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A, an amino acid sequence set forth in Table 1B (or a variant thereof) or Formula B, or an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C, such AAV capsid polypeptides, nucleic acid molecules encoding such vectors, nucleic acid molecules encoding such AAV capsid polypeptides, host cells containing and / or expressing such nucleic acid molecules, and methods and materials for making or using such vectors and / or AAV capsid polypeptides are provided.

Description

[0001] ADENO-ASSOCIATED VIRUS VECTORS FOR NUCLEIC ACID DELIVERY TO RETINAL CELLS, FOR NUCLEIC ACID DELIVERY ACROSS RETINAL REGIONS, OR FOR NUCLEIC ACID DELIVERY TO RETINAL GANGLION CELLS AND / OR RETINAL PIGMENT EPITHELIUM CELLS

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Application Serial No. 63 / 540,819, filed September 27, 2023, and the benefit of U.S. Provisional Application Serial No. 63 / 540,862, filed September 27, 2023, and the benefit of U.S. Provisional Application Serial No. 63 / 540,835, filed September 27, 2023. The disclosures of the prior applications are considered part of the disclosure of this application, and are incorporated in its entirety into this application

[0004] STATEMENT REGARDING FEDERAL FUNDING

[0005] This invention was made with government support under MH120094 awarded by the National Institutes of Health. The government has certain rights in the invention.

[0006] TECHNICAL FIELD

[0007] This document relates to adeno-associated virus (AAV) vectors. For example, this document provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having (a) the ability to deliver nucleic acid to foveal cones, (b) an increased efficiency to deliver nucleic acid to retinal cells, (c) the ability to deliver nucleic acid to retinal cells and drive high expression levels of nucleic acid within retinal cells, (d) the ability to deliver nucleic acid to retinal cells across retinal regions (e.g., across at least two retinal regions), (e) the ability to deliver nucleic acid to retinal cells of the parafovea region of the eye, (f) the ability to deliver nucleic acid to two or more different retinal cell types within an eye, (g) the ability to deliver nucleic acid to retinal pigment epithelial (RPE) cells, (h) an increased efficiency to deliver nucleic acid to photoreceptor cells of the retina, (i) an increased efficiency to deliver nucleic acid to retinal ganglion cells of the retina and / or retinal pigment epithelium cells of the retina, (j) an increased efficiency to deliver nucleic acid to bipolar cells of the retina, (k) an increased efficiency to deliver nucleic acid to OFF-retinal ganglion cells, and / or (1) increased packaging efficiency and the ability to deliver nucleic acid to cells (e.g., retinal cells). BACKGROUND

[0008] Viral vectors, such as AAV vectors, are efficient vehicles for in vivo nucleic acid delivery, and their use in the clinic is expanding. Improved AAV vectors and AAV production techniques for making effective AAV vector preparations should further expand the use of AAV vectors in the laboratory and clinic.

[0009] SUMMARY

[0010] This document provides AAV vectors (e.g., AAV2 vectors). For example, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal cells.

[0011] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 2 percent greater than, at least 2.5 percent greater than, at least 5 percent greater than, at least 7.5 percent greater than, at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in retinal cells of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara etal., Sci. Transl. Med., 5(189):189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells).

[0012] In another example, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) across retinal regions (e.g., across at least two retinal regions) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal cells across retinal regions and drive expression of delivered nucleic acid within the retinal cells. For example, the AAV vectors (e.g., AAV2 vectors) described herein can deliver nucleic acid to at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the fovea region, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the parafovea region, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the vascular arcade region, and / or at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the periphery region.

[0013] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) across retinal regions (e g., across at least two retinal regions) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the fovea region, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the parafovea region, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the vascular arcade region, and / or at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the periphery region of an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal cells of the fovea region, the parafovea region, the vascular arcade region, and / or the periphery region of an eye of a mammal (e g., a human or a non-human primate) that is greater than the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in retinal cells of those regions in a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can be used in place of the 7m8 AAV2 vector (Dalkara etal., Set. Transl. Med., 5(189):189ra76 (2013) and Bennett etal., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells).

[0014] In another example, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can have the ability to infect retinal ganglion cells and / or retinal pigment epithelium cells in vivo and deliver exogenous nucleic acid to the infected retinal ganglion cells and / or retinal pigment epithelium cells such that the infected retinal ganglion cells and / or retinal pigment epithelium cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal ganglion cells and / or retinal pigment epithelium cells.

[0015] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can have the ability to infect retinal ganglion cells and / or retinal pigment epithelium cells in vivo and deliver exogenous nucleic acid to the infected retinal ganglion cells and / or retinal pigment epithelium cells such that the infected retinal ganglion cells and / or retinal pigment epithelium cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of retinal ganglion cells and / or retinal pigment epithelium cells of an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal ganglion cells and / or retinal pigment epithelium cells of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e g., a wild-type AAV2 vector) in retinal ganglion cells and / or retinal pigment epithelium cells of an eye of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can be used in place of the 7m8 AAV2 vector (Dalkara etal., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett el al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to photoreceptor cells of the retina.

[0016] In general, one aspect of this document features AAV vectors (e.g., AAV2 vectors). For example, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect foveal cones in vivo and deliver exogenous nucleic acid to the infected foveal cones such that the infected foveal cones express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to foveal cones.

[0017] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect foveal cones in vivo and deliver exogenous nucleic acid to the infected foveal cones such that the infected foveal cones express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in cone cells present in the fovea of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in foveal cones of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in foveal cones of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to foveal cones.

[0018] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid at high levels. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal cells and drive high expression levels of nucleic acid within retinal cells.

[0019] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid at high levels. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least 2 percent (e.g., at least 2.5 percent, at least 5 percent, at least 7.5 percent, at least 10 percent, or at least 25 percent) of retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) in an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 2 percent greater than, at least 2.5 percent greater than, at least 5 percent greater than, at least 7.5 percent greater than, at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in retinal cells of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett el al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells). In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) across retinal regions (e.g., across at least two retinal regions) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal cells across retinal regions and drive expression of delivered nucleic acid within the retinal cells. For example, the AAV vectors (e.g., AAV2 vectors) described herein can deliver nucleic acid to at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the fovea region, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the parafovea region, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the vascular arcade region, and / or at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the periphery region.

[0020] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) across retinal regions (e.g., across at least two retinal regions) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the fovea region, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the parafovea region, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the vascular arcade region, and / or at least about 2 percent (e g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells in the periphery region of an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal cells of the fovea region, the parafovea region, the vascular arcade region, and / or the periphery region of an eye of a mammal (e.g., a human or a non-human primate) that is greater than the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in retinal cells of those regions in a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara etal., Sci. TrcmsL Med., 5(189):189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells).

[0021] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect retinal cells of the parafovea region of the eye in vivo and deliver exogenous nucleic acid to the infected retinal cells of the parafovea region such that the infected retinal cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal cells of the parafovea region of the eye.

[0022] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect retinal cells of the parafovea region of the eye in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells present in the parafovea region of an eye of a mammal (e.g., a human or a nonhuman primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal cells of the parafovea region of the eye of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in retinal cells of the parafovea region of the eye of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. TransL Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) of the parafovea region of the eye.

[0023] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect two or more (e.g., two or more, three or more, four or more, five or more, six or more, or seven or more) different retinal cell types within an eye in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to two or more (e g., two or more, three or more, four or more, five or more, six or more, or seven or more) different retinal cell types within an eye and drive expression of delivered nucleic acid within those retinal cells. For example, the AAV vectors (e.g., AAV2 vectors) described herein can deliver nucleic acid to two, three, four, five, six, or seven of the following retinal cell types of an eye: retinal ganglion cells, amacrine cells, horizontal cells, bipolar cells, Muller glia cells, photoreceptor cells, and retinal pigment epithelial (RPE) cells. In some cases, an AAV vector (e.g., an AAV2 vector) described herein can deliver nucleic acid to at least some (e.g., at least 2 percent, at least 2.5 percent, at least 5 percent, at least 10 percent, or at least 25 percent) of the retinal ganglion cells, amacrine cells, horizontal cells, bipolar cells, Muller glia cells, photoreceptor cells, and RPE cells of an eye of a mammal (e.g., a human or a non-human primate) following an intravitreal administration.

[0024] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have the ability to infect two or more (e.g., two or more, three or more, four or more, five or more, six or more, or seven or more) different retinal cell types within an eye in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal ganglion cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the amacrine cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the horizontal cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the bipolar cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the Muller glia cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the photoreceptor cells, and / or at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the RPE cells of an eye of a mammal (e.g., a human or a non-human primate) following, for example, an intravitreal administration. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal ganglion cells, amacrine cells, horizontal cells, bipolar cells, Muller glia cells, photoreceptor cells, and / or RPE cells of an eye of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in those retinal cells in a control mammal (e.g., a control human or a control non- human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10 :e64175 (2021)) to deliver nucleic acid to two or more (e.g., two or more, three or more, four or more, five or more, six or more, or seven or more) different retinal cell types within an eye of a mammal (e.g., a human or a non- human primate).

[0025] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have the ability to infect RPE cells in vivo and deliver exogenous nucleic acid to the infected RPE cells such that the infected RPE cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to RPE cells and drive expression of delivered nucleic acid within the RPE cells. For example, the AAV vectors (e.g., AAV2 vectors) described herein can deliver nucleic acid to at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the RPE cells of an eye of a mammal after, for example, an intravitreal administration.

[0026] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect RPE cells in vivo and deliver exogenous nucleic acid to the infected RPE cells such that the infected RPE cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the RPE cells of an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in RPE cells of an eye of a mammal (e g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild type AAV2 vector) in RPE cells in a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara el al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to RPE cells.

[0027] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect photoreceptor cells of the retina in vivo and deliver exogenous nucleic acid to the infected photoreceptor cells such that the infected photoreceptor cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to photoreceptor cells of the retina.

[0028] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect photoreceptor cells of the retina in vivo and deliver exogenous nucleic acid to the infected photoreceptor cells such that the infected photoreceptor cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of photoreceptor cells of an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in photoreceptor cells of the retina of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in photoreceptor cells of the retina of a control mammal (e.g., a control human or a control non- human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to photoreceptor cells of the retina.

[0029] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect retinal ganglion cells in vivo and deliver exogenous nucleic acid to the infected retinal ganglion cells such that the infected retinal ganglion cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal ganglion cells.

[0030] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have the ability to infect retinal ganglion cells in vivo and deliver exogenous nucleic acid to the infected retinal ganglion cells such that the infected retinal ganglion cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of retinal ganglion cells of an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal ganglion cells of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO:1 (e.g., a wild-type AAV2 vector) in retinal ganglion cells of an eye of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Ozturk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to photoreceptor cells of the retina.

[0031] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect bipolar cells of the retina in vivo and deliver exogenous nucleic acid to the infected bipolar cells such that the infected retinal bipolar cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to bipolar cells of the retina.

[0032] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have the ability to infect bipolar cells of the retina in vivo and deliver exogenous nucleic acid to the infected bipolar cells such that the infected bipolar cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of bipolar cells of the retina of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in bipolar cells of the retina of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO:1 (e.g., a wild-type AAV2 vector) in bipolar cells of the retina of a control mammal (e g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Ozturk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to photoreceptor cells of the retina.

[0033] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1 A (or a variant thereof) or Formula A can have the ability to infect OFF-retinal ganglion cells in vivo and deliver exogenous nucleic acid to the infected OFF-retinal ganglion cells such that the infected OFF- retinal ganglion cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to OFF-retinal ganglion cells.

[0034] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have the ability to infect OFF-retinal ganglion cells in vivo and deliver exogenous nucleic acid to the infected OFF-retinal ganglion cells such that the infected OFF- retinal ganglion cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of OFF-retinal ganglion cells of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in OFF-retinal ganglion cells of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e g., a wild-type AAV2 vector) in OFF- retinal ganglion cells of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett el al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Ozturk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to photoreceptor cells of the retina.

[0035] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have increased packaging efficiency, the ability to infect cells (e.g., retinal cells) in vivo or in vitro, and the ability to deliver exogenous nucleic acid to the infected cells such that the infected cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having increased packaging efficiency, the ability to deliver nucleic acid to cells (e.g., retinal cells) in vivo or in vitro, and the ability to drive expression of delivered nucleic acid within the cells. For example, the AAV vectors (e.g., AAV2 vectors) described herein can have a packaging efficiency greater than that of a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild type AAV2 vector).

[0036] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have increased packaging efficiency (e.g., package efficiency greater than that of a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild type AAV2 vector)), the ability to infect cells (e.g., retinal cells) in vivo or in vitro, and the ability to drive exogenous nucleic acid to the infected cells such that the infected cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have a packaging efficiency that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the packaging efficiency of a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: l(e.g., a wild-type AAV2 vector). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1A (or a variant thereof) or Formula A can have a packaging efficiency greater than that of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or the K912 AAV2 vector (Ozturk et al., eLife, 10:e64175 (2021)).

[0037] In general, one aspect of this document features an adeno-associated virus (AAV) vector (e.g., an AAV2 vector) comprising an AAV capsid polypeptide, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 582 and 583 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 586 and 587 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 590 and 591 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:2. The vector can be an AAV2 vector. The vector can infect greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a nonhuman primate). The vector can comprise an exogenous nucleic acid encoding an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more nucleic acid in retinal cells than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1.

[0038] In another aspect, this document features an AAV capsid polypeptide comprising the amino acid sequence of any one of SEQ ID NOs:2-5. The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 584 and 585 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 585 and 586 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 588 and 589 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 590 and 591 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 591 and 592 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:2-5. The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence, e.g., SEQ ID NOTO) are replaced with the amino acid sequence of SEQ ID NO:2. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOsT 1-26. An AAV vector comprising the polypeptide can infect greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). An AAV vector comprising the polypeptide can express more nucleic acid in retinal cells than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NOT.

[0039] In another aspect, this document features a nucleic acid molecule encoding an adeno- associated virus (AAV) vector comprising an AAV capsid polypeptide, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 587 and 588 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence, e.g., SEQ ID NOTO). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOT O or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 588 and 589 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 590 and 591 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 592 and 593 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs: 11-26. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:2-5. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:27-42. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:2. The vector can be an AAV2 vector. The vector can infect greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a nonhuman primate). The vector can comprise an exogenous nucleic acid encoding an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more nucleic acid in retinal cells than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1. The nucleic acid molecule can be DNA. In another aspect, this document features a nucleic acid molecule encoding an AAV capsid polypeptide comprising the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 583 and 584 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 587 and 588 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 590 and 591 of SEQ ID NO (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:l 1-42. The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:2. An AAV vector comprising the polypeptide can infect greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). An AAV vector comprising the polypeptide can express more nucleic acid in retinal cells than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1. The nucleic acid molecule can be DNA. In another aspect, this document features a host cell comprising a nucleic acid molecule of either of the two preceding paragraphs. The host cell can express the vector. The host cell can express the polypeptide.

[0040] In another aspect, this document features a host cell comprising an AAV vector comprising an AAV capsid polypeptide, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 582 and 583 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 586 and 587 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 590 and 591 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acids from position 585 to 590 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:2. The capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:l 1-42. The vector can be an AAV2 vector. The vector can infect greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). The vector can comprise an exogenous nucleic acid encoding an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more nucleic acid in retinal cells than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1. The host cell can be a retinal cell.

[0041] In another aspect, this document features a host cell comprising an AAV capsid polypeptide comprising the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 583 and 584 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 587 and 588 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 590 and 591 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:2-5. The polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:2. The capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs: 11-42. An AAV vector comprising the polypeptide can infect greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of the vector is administered intravitr eally to an eye of a human (or a non-human primate). An AAV vector comprising the polypeptide can express more nucleic acid in retinal cells than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1. The host cell can be a retinal cell.

[0042] In another aspect, this document features a composition comprising an AAV vector comprising an AAV capsid polypeptide, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 582 and 583 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 586 and 587 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 590 and 591 of SEQ ID NO (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acids from position 585 to 590 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:2. The capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:l 1-42. The vector can be an AAV2 vector. The vector can infect greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). The vector can comprise an exogenous nucleic acid encoding an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more nucleic acid in retinal cells than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:1. The composition can comprise from about 1 x 107to about 1 x 1014of the vector. The composition can comprise phosphate buffered saline, Hank’s Balanced Salt Solution, or Pluronic F68.

[0043] In another aspect, this document features a method for delivering an exogenous nucleic acid sequence to a retinal cell within a mammal. The method comprises (or consists essentially of, or consists of) contacting the retinal cell with an AAV vector comprising an AAV capsid polypeptide and the exogenous nucleic acid sequence, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5, wherein the AAV vector infects the retinal cell, thereby delivering the exogenous nucleic acid sequence to the retinal cell. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 583 and 584 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 587 and 588 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 590 and 591 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 591 and 592 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:2. The capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:l 1-42. The mammal can be a human (or a non-human primate). The vector can be an AAV2 vector. The vector can infect greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). The exogenous nucleic acid sequence can encode an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more of the exogenous nucleic acid sequence in the retinal cell than the level of expression in a retinal cell from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:1. The method can comprise intravitreally administering a composition comprising the vector to the mammal, thereby contacting the retinal cell with the vector. The composition can comprise from about 1 x 107to about 1 x 1014of the vector.

[0044] In another aspect, this document features a method for treating a retinal condition. The method comprises (or consists essentially of, or consists of) contacting retinal cells of a mammal having the retinal condition with AAV vectors comprising an AAV capsid polypeptide and an exogenous nucleic acid sequence, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5, wherein the AAV vectors infect the retinal cells and drive expression of the exogenous nucleic acid sequence within the retinal cells, thereby treating the retinal condition. The mammal can be a human (or a non-human primate). The retinal condition can be selected from the group consisting of LCA, OCA1, retinitis pigmentosa, rod / cone dystrophy, cone dystrophy, Stargardt Disease, Usher syndrome, XLRP, and XLRS. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1 ) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 584 and 585 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 587 and 588 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOT O or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 588 and 589 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 590 and 591 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 592 and 593 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of SEQ ID NO:5 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:2-5. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence SEQ ID NO:2. The capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs: 1 1 -42. The vectors can be AAV2 vectors. The vectors can infect greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of the vectors is administered intravitreally to an eye of the mammal. The exogenous nucleic acid sequence can encode an RNA. The RNA can be an siRNA or a microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, and an NR2E3 polypeptide. The vectors can express more of the exogenous nucleic acid sequence in the retinal cells than the level of expression in retinal cells from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NOT. The method can comprise intravitreally administering a composition comprising the vectors to the mammal, thereby contacting the retinal cells with the vectors. The composition can comprise from about 1 x 107to about 1 x 1014of the vectors. In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid at high levels. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal cells and drive high expression levels of nucleic acid within retinal cells.

[0045] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid at high levels. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least 2 percent (e.g., at least 2.5 percent, at least 5 percent, at least 7.5 percent, at least 10 percent, or at least 25 percent) of retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) in an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 2 percent greater than, at least 2.5 percent greater than, at least 5 percent greater than, at least 7.5 percent greater than, at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in retinal cells of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells).

[0046] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect retinal cells of the parafovea region of the eye in vivo and deliver exogenous nucleic acid to the infected retinal cells of the parafovea region such that the infected retinal cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal cells of the parafovea region of the eye.

[0047] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect retinal cells of the parafovea region of the eye in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. In some cases, an AAV vector (e g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells present in the parafovea region of an eye of a mammal (e.g., a human or a nonhuman primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal cells of the parafovea region of the eye of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in retinal cells of the parafovea region of the eye of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Ozttirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to retinal cells (e.g., retinal ganglion cells, photoreceptor cells, and bipolar cells) of the parafovea region of the eye.

[0048] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect retinal ganglion cells in vivo and deliver exogenous nucleic acid to the infected retinal ganglion cells such that the infected retinal ganglion cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal ganglion cells.

[0049] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect retinal ganglion cells in vivo and deliver exogenous nucleic acid to the infected retinal ganglion cells such that the infected retinal ganglion cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of retinal ganglion cells of an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal ganglion cells of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO:1 (e.g., a wild-type AAV2 vector) in retinal ganglion cells of an eye of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Ozturk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to photoreceptor cells of the retina.

[0050] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect OFF-retinal ganglion cells in vivo and deliver exogenous nucleic acid to the infected OFF-retinal ganglion cells such that the infected OFF- retinal ganglion cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to OFF-retinal ganglion cells.

[0051] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can have the ability to infect OFF-retinal ganglion cells in vivo and deliver exogenous nucleic acid to the infected OFF-retinal ganglion cells such that the infected OFF- retinal ganglion cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of OFF-retinal ganglion cells of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in OFF-retinal ganglion cells of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in OFF- retinal ganglion cells of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table IB (or a variant thereof) or Formula B can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2):107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to photoreceptor cells of the retina.

[0052] In general, one aspect of this document features an adeno-associated virus (AAV) vector (e.g., an AAV2 vector) comprising an AAV capsid polypeptide, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 587 and 588 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence, e.g., SEQ ID NO: 10). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 588 and 589 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 590 and 591 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 592 and 593 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID N0s:85-100. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOT O or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:77- 80. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs: 101-l 16. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1 ) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO: 80. The vector can be an AAV2 vector. The vector can infect greater than 2 percent of retinal cells within two or more retinal regions when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). The vector can comprise an exogenous nucleic acid encoding an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more nucleic acid in retinal cells in at least two retinal regions than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, wherein the at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region.

[0053] In another aspect, this document features an AAV capsid polypeptide (e.g., an AAV2 capsid polypeptide) comprising the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 583 and 584 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 587 and 588 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 590 and 591 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 591 and 592 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:80. An AAV vector comprising the polypeptide can infect greater than 2 percent of retinal cells within two or more retinal regions when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). An AAV vector comprising the polypeptide can express more nucleic acid in retinal cells in at least two retinal regions than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, wherein the at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region.

[0054] In another aspect, this document features a nucleic acid molecule encoding an AAV vector comprising an AAV capsid polypeptide, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 582 and 583 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 586 and 587 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 590 and 591 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs: 77-80 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acids from position 585 to 590 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO: 80. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:85-l 16. The vector can be an AAV2 vector. The vector can infect greater than 2 percent of retinal cells within two or more retinal regions when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). The vector can comprise an exogenous nucleic acid encoding an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more nucleic acid in retinal cells in at least two retinal regions than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1 , wherein the at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region. The nucleic acid molecule can be DNA.

[0055] In another aspect, this document features a nucleic acid molecule encoding an AAV capsid polypeptide comprising the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 583 and 584 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 587 and 588 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 590 and 591 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 591 and 592 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:80. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:85-l 16. An AAV vector comprising the polypeptide can infect greater than 2 percent of retinal cells within two or more retinal regions when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). An AAV vector comprising the polypeptide can express more nucleic acid in retinal cells in at least two retinal regions than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, wherein the at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region. The nucleic acid molecule can be DNA.

[0056] In another aspect, this document features a host cell comprising a nucleic acid molecule of either of the two preceding paragraphs. The host cell can express the vector. The host cell can express the polypeptide.

[0057] In another aspect, this document features a host cell comprising an AAV vector comprising an AAV capsid polypeptide, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 582 and 583 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 586 and 587 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 590 and 591 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acids from position 585 to 590 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO: 80. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:85-l 16. The vector can be an AAV2 vector. The vector can infect greater than 2 percent of retinal cells within two or more retinal regions when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). The vector can comprise an exogenous nucleic acid encoding an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more nucleic acid in retinal cells in at least two retinal regions than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:1, wherein the at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region. The host cell can be a retinal cell.

[0058] In another aspect, this document features a host cell comprising an AAV capsid polypeptide comprising the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 582 and 583 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 583 and 584 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 586 and 587 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 587 and 588 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 590 and 591 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 591 and 592 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1 ) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO:80. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:85-l 16. An AAV vector comprising the polypeptide can infect greater than 2 percent of retinal cells within two or more retinal regions when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). An AAV vector comprising the polypeptide can express more nucleic acid in retinal cells in at least two retinal regions than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, wherein the at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region. The host cell can be a retinal cell.

[0059] In another aspect, this document features a composition comprising an AAV vector comprising an AAV capsid polypeptide, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 582 and 583 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 586 and 587 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 590 and 591 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acids from position 585 to 590 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO: 80. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:85-l 16. The vector can be an AAV2 vector. The vector can infect greater than 2 percent of retinal cells within two or more retinal regions when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). The vector can comprise an exogenous nucleic acid encoding an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more nucleic acid in retinal cells in at least two retinal regions than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:1, wherein the at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region. The composition can comprise from about 1 x 107to about 1 x 1014of the vector. The composition can comprise phosphate buffered saline, Hank’s Balanced Salt Solution, or Pluronic F68.

[0060] In another aspect, this document features a method for delivering an exogenous nucleic acid sequence to retinal cells within at least two different retinal regions of an eye of a mammal. The method comprises (or consists essentially of, or consists of) contacting the retinal cells with an AAV vector comprising an AAV capsid polypeptide and the exogenous nucleic acid sequence, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80, wherein the AAV vector infects retinal cells within the at least two different retinal regions, thereby delivering the exogenous nucleic acid sequence to the retinal cells, wherein the at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 582 and 583 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 586 and 587 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 590 and 591 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO: 80. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:85-l 16. The mammal can be a human (or a non-human primate). The vector can be an AAV2 vector. The vector can infect greater than 2 percent of retinal cells within the at least two retinal regions when a titer of at least 1 x 107of the vector is administered intravitreally to an eye of a human (or a non-human primate). The exogenous nucleic acid sequence can encode an RNA or a polypeptide. The exogenous nucleic acid can encode an RNA. The RNA can be an siRNA or microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide. The vector can express more of the exogenous nucleic acid sequence in the retinal cells of the at least two retinal regions than the level of expression in a retinal cell from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1. The method can comprise intravitreally administering a composition comprising the vector to the mammal, thereby contacting the retinal cells with the vector. The composition can comprise from about 1 x 107to about 1 x 1014of the vector.

[0061] In another aspect, this document features a method for treating a retinal condition. The method comprises (or consists essentially of, or consists of) contacting retinal cells of at least two retinal regions of an eye of a mammal having the retinal condition with AAV vectors comprising an AAV capsid polypeptide and an exogenous nucleic acid sequence, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 77-80, and an NR2E3 polypeptide, wherein the AAV vectors infect the retinal cells of the at least two retinal regions and drive expression of the exogenous nucleic acid sequence within the retinal cells of the at least two retinal regions, thereby treating the retinal condition. The mammal can be a human (or a non-human primate). The retinal condition can be selected from the group consisting of LCA, 0CA1, retinitis pigmentosa, rod / cone dystrophy, cone dystrophy, Stargardt Disease, Usher syndrome, XLRP, and XLRS. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 582 and 583 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 586 and 587 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs: 77-80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 590 and 591 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs: 77-80 is located between amino acid positions 591 and 592 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs: 77-80 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO:80 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acids from position 585 to 590 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of any one of SEQ ID NOs:77-80. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acids from position 585 to 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence) are replaced with the amino acid sequence of SEQ ID NO: 80. In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs:85-l 16. The vectors can be AAV2 vectors. The vectors can infect greater than 2 percent of retinal cells in the at least two retinal regions when a titer of at least 1 x 107of the vectors is administered intravitreally to an eye of the mammal. The exogenous nucleic acid sequence can encode an RNA. The RNA can be an siRNA or a microRNA. The exogenous nucleic acid can encode a polypeptide. The polypeptide can be an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, and an NR2E3 polypeptide. The vectors can express more of the exogenous nucleic acid sequence in the retinal cells of the at least two retinal regions than the level of expression in retinal cells of the at least two retinal regions from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1. The method can comprise intravitreally administering a composition comprising the vectors to the mammal, thereby contacting the retinal cells of the at least two retinal regions with the vectors. The composition can comprise from about 1 x 107to about 1 x 1014of the vectors. The at least two retinal regions can be selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region.

[0062] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can have the ability to infect retinal cells (e.g., retinal ganglion cells, retinal pigment epithelium cells, photoreceptor cells, and bipolar cells) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid at high levels. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal cells and drive high expression levels of nucleic acid within retinal cells.

[0063] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can have the ability to infect retinal cells (e.g., retinal ganglion cells, retinal pigment epithelium cell, photoreceptor cells, and bipolar cells) in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid at high levels. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least 2 percent (e.g., at least 2.5 percent, at least 5 percent, at least 7.5 percent, at least 10 percent, or at least 25 percent) of retinal cells (e.g., retinal ganglion cells, retinal pigment epithelium cells, photoreceptor cells, and bipolar cells) in an eye of a mammal (e.g., a human or a non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal cells (e.g., retinal ganglion cells, retinal pigment epithelium cells, photoreceptor cells, and bipolar cells) of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 2 percent greater than, at least 2.5 percent greater than, at least 5 percent greater than, at least 7.5 percent greater than, at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in retinal cells of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Ozturk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to retinal cells (e.g., retinal ganglion cells, retinal pigment epithelium cells, photoreceptor cells, and bipolar cells).

[0064] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can have the ability to infect retinal cells of the parafovea region of the eye in vivo and deliver exogenous nucleic acid to the infected retinal cells of the parafovea region such that the infected retinal cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to retinal cells of the parafovea region of the eye.

[0065] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can have the ability to infect retinal cells of the parafovea region of the eye in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal cells present in the parafovea region of an eye of a mammal (e.g., a human or a nonhuman primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal cells of the parafovea region of the eye of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in retinal cells of the parafovea region of the eye of a control mammal (e.g., a control human or a control non-human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can be used in place of the 7m8 AAV2 vector (Dalkara et al., Sci. Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Ozturk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to retinal cells (e.g., retinal ganglion cells, retinal pigment epithelium cells, photoreceptor cells, and bipolar cells) of the parafovea region of the eye.

[0066] In another aspect, this document provides AAV vectors (e.g., AAV2 vectors) containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C. The AAV vectors (e.g., AAV2 vectors) described herein containing a capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can have the ability to infect two or more (e.g., two or more, three or more, four or more, five or more, six or more, or seven or more) different retinal cell types within an eye in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. This document also provides methods and materials for making and using AAV vectors (e.g., AAV2 vectors) having the ability to deliver nucleic acid to two or more (e.g., two or more, three or more, four or more, five or more, six or more, or seven or more) different retinal cell types within an eye and drive expression of delivered nucleic acid within those retinal cells. For example, the AAV vectors (e.g., AAV2 vectors) described herein can deliver nucleic acid to two, three, four, five, six, or seven of the following retinal cell types of an eye: retinal ganglion cells, amacrine cells, horizontal cells, bipolar cells, Muller glia cells, photoreceptor cells, and retinal pigment epithelial (RPE) cells. In some cases, an AAV vector (e.g., an AAV2 vector) described herein can deliver nucleic acid to at least some (e.g., at least 2 percent, at least 2.5 percent, at least 5 percent, at least 10 percent, or at least 25 percent) of the retinal ganglion cells, amacrine cells, horizontal cells, bipolar cells, Muller glia cells, photoreceptor cells, and RPE cells of an eye of a mammal (e.g., a human or a non-human primate) following an intravitreal administration.

[0067] As described herein, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can have the ability to infect two or more (e.g., two or more, three or more, four or more, five or more, six or more, or seven or more) different retinal cell types within an eye in vivo and deliver exogenous nucleic acid to the infected retinal cells such that the infected retinal cells express the exogenous nucleic acid. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to infect and drive mRNA expression of an exogenous nucleic acid in at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the retinal ganglion cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the amacrine cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the horizontal cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the bipolar cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the Muller glia cells, at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the photoreceptor cells, and / or at least about 2 percent (e.g., at least about 2.5 percent, at least about 5 percent, at least about 7.5 percent, at least about 10 percent, or at least about 25 percent) of the RPE cells of an eye of a mammal (e.g., a human or a non-human primate) following, for example, an intravitreal administration. In some cases, an AAV vector (e.g., an AAV2 vector) provided herein can have the ability to drive a level of mRNA expression of an exogenous nucleic acid in retinal ganglion cells, amacrine cells, horizontal cells, bipolar cells, Muller glia cells, photoreceptor cells, and / or RPE cells of an eye of a mammal (e.g., a human or a non-human primate) that is greater than (e.g., at least 10 percent greater than, at least 25 percent greater than, at least 50 percent greater than, at least 75 percent greater than, or at least 100 percent greater than) the level of mRNA expression of an exogenous nucleic acid driven by a comparable AAV vector having an AAV capsid polypeptide that consists of the amino acid sequence of SEQ ID NO: 1 (e.g., a wild-type AAV2 vector) in those retinal cells in a control mammal (e.g., a control human or a control non- human primate). In some cases, an AAV vector (e.g., an AAV2 vector) provided herein having an AAV capsid polypeptide that includes an amino acid sequence set forth in Table 1C (or a variant thereof) or Formula C can be used in place of the 7m8 AAV2 vector (Dalkara et al., Set Transl. Med., 5(189): 189ra76 (2013) and Bennett et al., J. Struct. Biol., 209(2): 107433 (2020)) or in place of the K912 AAV2 vector (Oztiirk et al., eLife, 10:e64175 (2021)) to deliver nucleic acid to two or more (e.g., two or more, three or more, four or more, five or more, six or more, or seven or more) different retinal cell types within an eye of a mammal (e.g., a human or a non- human primate).

[0068] In general, one aspect of this document features an adeno-associated virus (AAV) vector (e.g., an AAV2 vector) comprising an AAV capsid polypeptide, wherein the capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 151-154. The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:151-154 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:151-154 is located between amino acid positions 581 and 582 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:151-154 is located between amino acid positions 582 and 583 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 583 and 584 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 584 and 585 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:151-154 is located between amino acid positions 585 and 586 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 586 and 587 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 587 and 588 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence, e.g. SEQ ID NOTO). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NOT (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 588 and 589 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NOT) except that the amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 589 and 590 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs:151-154 is located between amino acid positions 590 and 591 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NOTO or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 591 and 592 of SEQ ID NOT (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO:1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 592 and 593 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO:1) except that the amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 593 and 594 of SEQ ID NO: 1 (or the appropriate amino acid positions of the alternative sequence). The capsid polypeptide can comprise the amino acid sequence of SEQ ID NO: 1 (or an alternative sequence that is the amino acid sequence set forth in SEQ ID NO: 10 or that is an amino acid sequence at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 1) except that the amino acid sequence of SEQ ID NO: 154 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO:1 (or the appropriate amino acid positions of the alternative sequence). In some cases, the capsid polypeptide can comprise or consist of the amino acid sequence of any of SEQ ID NOs: 159-174. The capsid polypeptide can comprise the...

Claims

WHAT IS CLAIMED IS:

1. An adeno-associated virus (AAV) vector comprising an AAV capsid polypeptide, wherein said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5, 77-80, and 151-154.

2. The vector of claim 1, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that said amino acid sequence of any one of SEQ ID NOs: 2-5, 77-80, and 151-154 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, betw een amino acid positions 584 and 585. between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588. between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NOT or SEQ ID NOTO.

3. The vector of claim 1, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that said amino acid sequence of SEQ ID NO:

5. 80, or 154 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584. between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 or SEQ ID NOTO.

4. The vector of claim 1, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that the amino acids from position 585 to 590 of SEQ ID NOT or SEQ ID NOTO are replaced with said amino acid sequence of any one of SEQ ID NOs:2-5, 77-80, and 151-154.

5. The vector of claim 1, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that the amino acids from position 585to 590 of SEQ ID NOT or SEQ ID NOTO are replaced with said amino acid sequence of SEQ ID NO:2, 80, or 154.

6. The vector of any one of claims 1-5, wherein said vector is an AAV2 vector.

7. The vector of any one of claims 1-6, wherein:(a) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5, and wherein said vector infects greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of said vector is administered intravitreally to an eye of a human;(b) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 77-80, and wherein said vector infects greater than 2 percent of retinal cells within two or more retinal regions when a titer of at least 1 x 107of said vector is administered intravitreally to an eye of a human; or(c) said capsid poly peptide comprises the amino acid sequence of any one of SEQ ID NOs: 151-154, and wherein said vector infects greater than 2 percent of retinal ganglion cells and / or retinal pigment epithelium cells of an eye when a titer of at least 1 x 107of said vector is administered intravitreally to said eye.

8. The vector of any one of claims 1-7, wherein said vector comprises an exogenous nucleic acid encoding an RNA or a polypeptide.

9. The vector of claim 8, wherein said exogenous nucleic acid encodes an RNA.

10. The vector of claim 9, wherein said RNA is an siRNA or microRNA.1 1. The vector of claim 8, wherein said exogenous nucleic acid encodes a polypeptide.

12. The vector of claim 11, wherein said polypeptide is an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide.

13. The vector of any one of claims 1-12, wherein:(a) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5. and wherein said vector expresses more nucleic acid in retinal cells than the level ofexpression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:1;(b) said capsid polypeptide comprises the ammo acid sequence of any one of SEQ ID NOs: 77-80, and wherein said vector expresses more nucleic acid in retinal cells in at least two retinal regions than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1, wherein said at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region; or(c) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 151-154, and wherein said vector expresses more nucleic acid in retinal ganglion cells and / or retinal pigment epithelium cells than the level of expression from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NOT.

14. The vector of any one of claims 1-13, wherein said capsid polypeptide comprises the amino acid sequence of any of SEQ ID NOs: 1 1-42. 85-116. or 159-190.

15. A composition comprising a vector of any one of claims 1-14 and a pharmaceutically acceptable excipient.

16. The composition of claim 15, wherein said composition comprises from about 1 x 107to about 1 x 1014of said vector.

17. The composition of any one of claims 15-16, wherein said pharmaceutically acceptable excipient comprises one or more of phosphate buffered saline. Hank’s Balanced Salt Solution, and Pluronic F68.

18. A method for (a) delivering an exogenous nucleic acid sequence to a retinal cell within a mammal, (b) delivering an exogenous nucleic acid sequence to retinal cells within at least two different retinal regions of an eye of a mammal, or (c) delivering an exogenous nucleic acid sequence to a retinal ganglion cell within a mammal, wherein said method comprises:(a) contacting said retinal cell with an AAV vector comprising an AAV capsid polypeptide and said exogenous nucleic acid sequence, wherein said capsid polypeptidecomprises the amino acid sequence of any one of SEQ ID NOs:2-5, wherein said AAV vector infects said retinal cell, thereby delivering said exogenous nucleic acid sequence to said retinal cell;(b) contacting said retinal cells with an AAV vector comprising an AAV capsid polypeptide and said exogenous nucleic acid sequence, wherein said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80, wherein said AAV vector infects retinal cells within said at least two different retinal regions, thereby delivering said exogenous nucleic acid sequence to said retinal cells, wherein said at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery' region; or(c) contacting said retinal ganglion cell with an AAV vector comprising an AAV capsid polypeptide and said exogenous nucleic acid sequence, wherein said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:151-154, wherein said AAV vector infects said photoreceptor cell, thereby delivering said exogenous nucleic acid sequence to said photoreceptor cell.

19. The method of claim 18, wherein said capsid polypeptide comprises:(a) the amino acid sequence of SEQ ID NO:1 or SEQ ID NOTO except that said amino acid sequence of any one of SEQ ID NOs:2-5 is located between amino acid positions 581 and 582. between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592. between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 or SEQ ID NOTO;(b) the amino acid sequence of SEQ ID NOT or SEQ ID NO: 10 except that said amino acid sequence of any one of SEQ ID NOs:77-80 is located between amino acid positions 581 and 582. between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590. between amino acid positions 590 and 591, between amino acidpositions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 or SEQ ID NO: 10; or(c) the ammo acid sequence of SEQ ID NO: 1 or SEQ ID NO: 10 except that said amino acid sequence of any one of SEQ ID NOs: 151-154 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586. between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 or SEQ ID NO: 10.

20. The method of claim 18, wherein said capsid polypeptide comprises:(a) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that said amino acid sequence of SEQ ID NO:5 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584. between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590. between amino acid positions 590 and 591, between amino acid positions 591 and 592. between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NOT or SEQ ID NOTO;(b) the amino acid sequence of SEQ ID NOT or SEQ ID NO: 10 except that said amino acid sequence of SEQ ID NO: 80 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590. between amino acid positions 590 and 591, between amino acid positions 591 and 592. between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NOT or SEQ ID NOTO; or(c) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that said amino acid sequence of SEQ ID NO: 154 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584,between amino acid positions 584 and 585, between amino acid positions 585 and 586. between amino acid positions 586 and 587, between amino acid positions 587 and 588. between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NOT or SEQ ID NO: 10.

21. The method of claim 18, wherein said capsid polypeptide comprises:(a) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 10 except that the amino acids from position 585 to 590 of SEQ ID NO: 1 or SEQ ID NO: 10 are replaced with said amino acid sequence of any one of SEQ ID NOs:2-5;(b) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 10 except that the amino acids from position 585 to 590 of SEQ ID NO: 1 or SEQ ID NOTO are replaced with said amino acid sequence of any one of SEQ ID NOs:77-80; or(c) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that the amino acids from position 585 to 590 of SEQ ID NO: 1 or SEQ ID NOTO are replaced with said amino acid sequence of any one of SEQ ID NOs: 151-154.

22. The method of claim 18, wherein said capsid polypeptide comprises:(a) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that the amino acids from position 585 to 590 of SEQ ID NO: 1 or SEQ ID NOTO are replaced with said amino acid sequence of SEQ ID NO:2;(b) the amino acid sequence of SEQ ID NOT or SEQ ID NOTO except that the amino acids from position 585 to 590 of SEQ ID NO: 1 or SEQ ID NO: 10 are replaced with said amino acid sequence of SEQ ID NO: 80; or(c) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that the amino acids from position 585 to 590 of SEQ ID NO: 1 or SEQ ID NOTO are replaced with said amino acid sequence of SEQ ID NOT 54.

23. The method of any one of claims 18-22, wherein said mammal is a human.

24. The method of any one of claims 18-23, wherein said vector is an AAV2 vector.

25. The method of any one of claims 18-24, wherein:(a) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5. and wherein said vector infects greater than 2.5 percent of retinal cells when a titer of at least 1 x 107of said vector is administered intravitreally to an eye of a human;(b) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80, and wherein said vector infects greater than 2 percent of retinal cells within said at least two retinal regions when a titer of at least 1 x 107of said vector is administered intravitreally to an eye of a human; or(c) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:151-154, and wherein said vector infects greater than 2 percent of retinal ganglion cells and / or retinal pigment epithelium cells of an eye when a titer of at least 1 x 107 of said vector is administered intravitreally to said eye.

26. The method of any one of claims 18-25, wherein said exogenous nucleic acid sequence encodes an RNA or a polypeptide.

27. The method of claim 26. wherein said exogenous nucleic acid encodes an RNA.

28. The method of claim 27, wherein said RNA is an siRNA or microRNA.

29. The method of claim 26, wherein said exogenous nucleic acid encodes a polypeptide.

30. The method of claim 29, wherein said polypeptide is an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide.

31. The method of any one of claims 18-30, wherein:(a) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5, and wherein said vector expresses more of said exogenous nucleic acid sequence in said retinal cell than the level of expression in a retinal cell from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1;(b) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80, and wherein said vector expresses more of said exogenous nucleic acid sequence in said retinal cells of said at least two retinal regions than the level of expression in a retinalcell from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1; or(c) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:151-154, and wherein said vector expresses more of said exogenous nucleic acid sequence in said retinal ganglion cell than the level of expression in a retinal ganglion cell from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1.

32. The method of any one of claims 18-31, wherein said method comprises intravitreally administering a composition comprising said vector to said mammal, thereby contacting (a) said retinal cell with said vector, (b) said retinal cells with said vector, or (c) said retinal ganglion cell with said vector.

33. The method of claim 32, wherein said composition comprises from about 1 x 107to about 1 x 1014of said vector.

34. A method for treating a retinal condition in a mammal in need thereof, wherein said method comprises:(a) contacting retinal cells of a mammal having said retinal condition with AAV vectors comprising an AAV capsid polypeptide and an exogenous nucleic acid sequence, wherein said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5, wherein said AAV vectors infect said retinal cells and drive expression of said exogenous nucleic acid sequence within said retinal cells, thereby treating said retinal condition;(b) contacting retinal cells of at least two retinal regions of an eye of a mammal having said retinal condition with AAV vectors comprising an AAV capsid polypeptide and an exogenous nucleic acid sequence, wherein said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80, wherein said AAV vectors infect said retinal cells of said at least two retinal regions and drive expression of said exogenous nucleic acid sequence within said retinal cells of said at least two retinal regions, thereby treating said retinal condition; or(c) contacting retinal ganglion cells and / or retinal pigment epithelium cells of a mammal having said retinal condition with AAV vectors comprising an AAV capsid polypeptide and an exogenous nucleic acid sequence, wherein said capsid polypeptidecomprises the amino acid sequence of any one of SEQ ID NOs: 151-154, wherein said AAV vectors infect said retinal ganglion cells and / or retinal pigment epithelium cells and drive expression of said exogenous nucleic acid sequence within said retinal ganglion cells and / or retinal pigment epithelium cells, thereby treating said retinal condition.

35. The method of claim 34, wherein said mammal is a human.

36. The method of any one of claims 34-35, wherein:(a) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5, and wherein said retinal condition is selected from the group consisting of LCA, OCA1, retinitis pigmentosa, rod / cone dystrophy, cone dystrophy. Stargardt Disease, Usher syndrome, XLRP, and XLRS;(b) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80, and wherein said retinal condition is selected from the group consisting of LCA, 0CA1, retinitis pigmentosa, rod / cone dystrophy, cone dystrophy, Stargardt Disease, Usher syndrome, XLRP, and XLRS; or(c) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 151-154, and wherein said retinal condition is selected from the group consisting of cone dystrophy, cone / rod dystrophy, retinitis pigmentosa, macular degeneration, achromatopsia, blue cone monochromacy. and color blindness.

37. The method of any one of claims 34-36, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that said amino acid sequence of any one of SEQ ID NOs:2-5, 77-80, and 151-154 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590. between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 or SEQ ID NOTO.

38. The method of any one of claims 34-36, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 10 except that said amino acidsequence of SEQ ID NO: 5, 80, or 154 is located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584. between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592. between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NO: 1 or SEQ ID NO: 10.

39. The method of any one of claims 34-36, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that the amino acids from position 585 to 590 of SEQ ID NO: 1 or SEQ ID NOTO are replaced with said amino acid sequence of any one of SEQ ID NOs:2-5, 77-80, and 151-154.

40. The method of any one of claims 34-36, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO except that the amino acids from position 585 to 590 of SEQ ID NO: 1 or SEQ ID NOTO are replaced with said amino acid sequence of SEQ ID NO:2, 80, or 154.

41. The method of any one of claims 34-40, wherein said vectors are AAV2 vectors.

42. The method of any one of claims 34-41, wherein:(a) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5. and wherein said vectors infect greater than 2.5 percent of retinal cells when a titer of at least I x IO7of said vectors is administered intravitreally to an eye of said mammal;(b) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80, and wherein said vectors infect greater than 2 percent of retinal cells in said at least two retinal regions when a titer of at least 1 x 107of said vectors is administered intravitreally to an eye of said mammal; or(c) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:151-154, and wherein said vectors infect greater than 2 percent of retinal ganglion cells and / or retinal pigment epithelium cells when a titer of at least 1 x 107of said vectors is administered intravitreally to an eye of said mammal.

43. The method of any one of claims 34-42, wherein said exogenous nucleic acid sequence encodes an RNA.

44. The method of claim 43, wherein said RNA is an siRNA or a microRNA.

45. The method of any one of claims 34-42, wherein said exogenous nucleic acid encodes a polypeptide.

46. The method of claim 45, wherein said polypeptide is an ABCA4 polypeptide, a CRB1 polypeptide, an NPHP5 polypeptide, or an NR2E3 polypeptide.

47. The method of any one of claims 34-46, wherein:(a) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5, and wherein said vectors express more of said exogenous nucleic acid sequence in said retinal cells than the level of expression in retinal cells from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NOT;(b) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80, and wherein said vectors express more of said exogenous nucleic acid sequence in said retinal cells of said at least two retinal regions than the level of expression in retinal cells of said at least two retinal regions from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 1; or(c) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 151-154, and wherein said vectors express more of said exogenous nucleic acid sequence in said retinal ganglion cells and / or retinal pigment epithelium cells than the level of expression in retinal ganglion cells and / or retinal pigment epithelium cells from a comparable AAV vector comprising a capsid polypeptide consisting of the amino acid sequence set forth in SEQ ID NOT.

48. The method of any one of claims 34-47, wherein:(a) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:2-5, and wherein said method comprises intravitreally administering a composition comprising said vectors to said mammal, thereby contacting said retinal cells with said vectors;(b) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:77-80, and wherein said method comprises intravitreally administering a composition comprising said vectors to said mammal, thereby contacting said retinal cells of said at least two retinal regions with said vectors, and optionally wherein said at least two retinal regions are selected from the group consisting of a fovea region, a parafovea region, a vascular arcade region, and a periphery region; or(c) said capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 151-154, and wherein said method comprises intravitreally administering a composition comprising said vectors to said mammal, thereby contacting said retinal ganglion cells and / or retinal pigment epithelium cells with said vectors.

49. The method of claim 48, wherein said composition comprises from about I x 107to about 1 x 1014of said vectors.

50. A non-naturally occurring adeno-associated virus (AAV) vector comprising an AAV capsid polypeptide, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO comprising an amino acid sequence insert of Formula A, Formula B, or Formula C located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585. between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NOT or SEQ ID NO: 10, wherein said Formula A is:-Ll-EGSGRN (SEQ ID NO:2)-L2-, wherein said LI and said L2 are each independently optional amino acid linkers having one, two, or three amino acids, wherein said Formula B is:-Ll-EHQTRP (SEQ ID NO:77)-L2-. wherein said LI and said L2 are each independently optional amino acid linkers having one, two, or three amino acids, and wherein said Formula C is:-Ll-NTEARV (SEQ ID NO: 151)-L2-, wherein said LI and said L2 are each independently optional amino acid linkers having one, two, or three amino acids.

51. The vector of claim 50, wherein said LI is one amino acid XL52. The vector of claim 51, wherein said XI is selected from the group of amino acid residues consisting of A, V, I, and L.

53. The vector of claim 54, wherein said XI is A.

54. The vector of claim 50, wherein said LI is two amino acids X2-X1.

55. The vector of claim 54, wherein said XI is selected from the group of amino acid residues consisting of A, V, I, and L.

56. The vector of claim 55, wherein said XI is A.

57. The vector of any one of claims 54-56. wherein said X2 is selected from the group of amino acid residues consisting of A, V, I, and L.

58. The vector of claim 57, wherein said X2 is L.

59. The vector of claim 54, wherein said X2-X1 is LA.

60. The vector of claim 50, wherein said LI is three amino acids X3-X2-X1.

61. The vector of claim 60, wherein said XI is selected from the group of amino acid residues consisting of A, V, I, and L.

62. The vector of claim 61, wherein said XI is A.

63. The vector of any one of claims 60-62, wherein said X2 is selected from the group of amino acid residues consisting of A, V, I, and L.

64. The vector of claim 63, wherein said X2 is L.

65. The vector of claim 60, wherein said X2-X1 is LA.

66. The vector of any one of claims 60-65. wherein said X3 is selected from the group of amino acid residues consisting of A, V, I, and L.

67. The vector of claim 50, wherein said LI is absent.

68. The vector of any one of claims 50-67, wherein said L2 is one amino acid Zl.

69. The vector of claim 68, wherein said Zl is selected from the group of amino acid residues consisting of A. V, I, and L.

70. The vector of claim 68, wherein said Zl is A.

71. The vector of any one of claims 50-67. wherein said L2 is two amino acids Z1-Z2.

72. The vector of claim 71, wherein said Zl is selected from the group of amino acid residues consisting of A, V, I, and L.

73. The vector of claim 71, wherein said Zl is A.

74. The vector of any one of claims 71-73, wherein said Z2 is selected from the group of amino acid residues consisting of A, V, I, and L.

75. The vector of claim 74, wherein said Z2 is L.

76. The vector of claim 75, wherein said Z1-Z2 is AL.

77. The vector of any one of claims 50-67. wherein said L2 is three amino acids Z1-Z2- Z378. The vector of claim 77, wherein said Zl is selected from the group of amino acid residues consisting of A. V, I, and L.

79. The vector of claim 78, wherein said Z1 is A.

80. The vector of any one of claims 77-79, wherein said Z2 is selected from the group of amino acid residues consisting of A, V, I, and L.

81. The vector of claim 80, wherein said Z2 is L.

82. The vector of claim 77, wherein said Z1-Z2 is AL.

83. The vector of any one of claims 77-82. wherein said Z3 is selected from the group of amino acid residues consisting of A. V, I, and L.

84. The vector of any one of claims 50-67, wherein said L2 is absent.

85. The vector of claim 50, wherein said amino acid sequence insert comprises any one of SEQ ID NOs:2-5, 77-80. and 151-154.

86. A non-naturally occurring AAV capsid polypeptide, wherein said capsid polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NOTO comprising an amino acid sequence insert of Formula A, Formula B, or Formula C located between amino acid positions 581 and 582, between amino acid positions 582 and 583, between amino acid positions 583 and 584, between amino acid positions 584 and 585, between amino acid positions 585 and 586, between amino acid positions 586 and 587, between amino acid positions 587 and 588, between amino acid positions 588 and 589, between amino acid positions 589 and 590, between amino acid positions 590 and 591, between amino acid positions 591 and 592, between amino acid positions 592 and 593, or between amino acid positions 593 and 594 of SEQ ID NOT or SEQ ID NOTO, wherein said Formula A is:-Ll-EGSGRN (SEQ ID NO:2)-L2-, wherein said LI and said L2 are each independently optional amino acid linkers having one, two, or three amino acids, wherein said Formula B is:-Ll-EHQTRP (SEQ ID NO:77)-L2-, wherein said LI and said L2 are each independently optional amino acid linkers having one, two, or three amino acids, and wherein said Formula C is:-Ll-NTEARV (SEQ ID NO: 151)-L2-,wherein said LI and said L2 are each independently optional amino acid linkers having one, two, or three amino acids.

87. A method for administering an exogenous nucleic acid sequence to a mammal in need thereof, wherein said method comprises administering an effective amount of a vector of any one of claims 50-85 to said mammal, wherein said vector comprising said exogenous nucleic acid sequence.

88. The method of claim 87, wherein said mammal is a human.

89. The method of any one of claims 87-88, wherein said administering comprises administering said effective amount to an eye of said mammal.

90. The method of any one of claims 87-89, wherein said administering is sufficient to allow for expression of said exogenous nucleic acid sequence in a cell of said mammal.

91. The method of any one of claims 87-90, wherein said exogenous nucleic acid sequence encodes a therapeutic polypeptide.

92. A method of treating a retinal disorder in a patient in need thereof, comprising administering to the patient’s eye an effective amount of an AAV vector, wherein the AAV vector comprises an AAV capsid polypeptide and an exogenous nucleic acid sequence, wherein the AAV capsid polypeptide comprises an amino acid sequence insert of Formula A, Formula B, or Formula C, wherein said Formula A is:-Ll-EGSGRN (SEQ ID NO:2)-L2-, wherein said LI and said L2 are each independently optional amino acid linkers having one, two, or three amino acids, wherein said Formula B is:-Ll-EHQTRP (SEQ ID NO:77)-L2-, wherein said LI and said L2 are each independently optional amino acid linkers having one, two, or three amino acids, and wherein said Formula C is:-Ll-NTEARV (SEQ ID NO: 151)-L2-,wherein said LI and said L2 are each independently optional amino acid linkers having one, two, or three amino acids.

Images