Peptide Ligands for Retinal Cell Targeting
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Solution Overview
Problem
Current gene therapy delivery methods for inherited retinal dystrophies, such as subretinal injection of viral vectors, pose risks and lack efficient, cost-effective solutions for targeting photoreceptors and retinal pigmented epithelial cells, leading to impaired vision or blindness in millions worldwide.
Innovation Solution
Development of a peptide compound with a specific structure that targets the retina, allowing for targeted delivery of therapeutic agents to photoreceptors, retinal pigmented epithelial cells, and Müller glia, potentially using lipid nanoparticles for improved safety and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If subretinal injection of viral vectors is used for gene therapy delivery, then therapeutic cargo can be delivered to retinal cells, but high risks are associated with the injection method
Solution Approach 1:
The patent uses peptide ligands as intermediary molecules that specifically bind to receptors on retinal cells (photoreceptors, RPE, Müller glia). These peptides are conjugated to therapeutic cargo or delivered via lipid nanoparticles, serving as a safe mediator that enables targeted delivery without requiring direct subretinal injection of viral vectors.
Solution Approach 2:
The patent replaces the mechanical injection system (needles, surgical procedures) with a biochemical delivery system. Therapeutic cargo is delivered through peptide-mediated targeting and lipid nanoparticle uptake, substituting mechanical trauma with gentle biochemical interactions that the retinal cells naturally accept.
2Reliability
If viral vectors are used for gene therapy, then robust delivery of therapeutic cargo is achieved, but cell-specific targeting is insufficient
Solution Approach 1:
The patent employs different peptide ligands with specific sequences designed to bind to receptors on different retinal cell types. For example, certain peptides target photoreceptors while others target RPE or Müller glia, allowing precise local delivery to specific cell populations within the retina rather than uniform distribution.
Solution Approach 2:
The patent modifies the chemical parameters of the delivery system by using peptide ligands with varying amino acid sequences, hydrophobicity, and binding affinities. These parameter changes enable selective binding to different cell surface receptors, achieving cell-specific targeting while maintaining robust delivery efficacy.
3Reliability
If existing delivery methods are used, then therapeutic treatment is provided, but cost-effective solutions are lacking
Solution Approach 1:
The patent uses peptide ligands and lipid nanoparticle carriers that can be synthesized more cheaply and efficiently than viral vectors. These components are designed for single-use delivery, eliminating the need for complex viral vector production facilities and extensive purification processes, thereby reducing manufacturing costs while maintaining treatment effectiveness.
Data Source
AI summary
Disclosed herein are peptides useful for targeting the retina, and may be useful for targeting specific cells in the retina. The peptides may have a Formula I or V:R1—X1—X2—(X3)n—X4—X5—X6—X7—R2 Formula IR1-Asn-Val-Ser-Ala-Tyr-Pro-Thr-R2 Formula V.Also disclosed are conjugates and compositions comprising the peptides. The compositions may comprise a desired agent to be delivered to the retina, such as a therapeutic agent and/or an imaging agent. Methods for administering the peptide, conjugates, and/or composition to a subject also are disclosed.