Myeloid Cell Gene Modulation for Retinal Neovascularization
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Solution Overview
Problem
Retinopathies, such as retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy, are characterized by retinal neovascularization driven by myeloid lineage cell activation, leading to progressive vision loss and blindness, with existing treatments only slowing progression and having undesirable side effects.
Innovation Solution
Administering agents such as siRNA, shRNA, or antisense oligonucleotides complementary to genes encoding factors like Spp1, Trem2, and STAT3, or using viral vectors like lentiviral or recombinant adeno-associated viral vectors, to inhibit their expression and activity, alongside increasing SOCS3 expression, to reduce myeloid cell activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If myeloid lineage cell activation is left untreated, then retinal neovascularization progresses leading to vision loss, but existing treatments only slow progression and have undesirable side effects
Solution Approach 1:
The patent extracts and targets specific activating factors (Spp1, Trem2, Tspo, STAT3) from the complex myeloid cell activation pathway. By identifying and eliminating these specific factors through complementary RNA agents, the invention directly addresses the harmful neovascularization process while preserving beneficial myeloid cell functions, thereby resolving the contradiction between vision preservation and preventing vision loss.
Solution Approach 2:
The patent changes the expression level parameter of specific factors (Spp1, Trem2, Tspo, STAT3) from high/activated state to low/inhibited state using complementary RNA agents. This parameter change selectively modulates myeloid cell activation, reducing harmful neovascularization while maintaining protective functions, thus resolving the treatment effectiveness versus side effects contradiction.
2Reliability
If factors like Spp1, Trem2, Tspo, and STAT3 are inhibited, then myeloid cell activation and neovascularization are reduced, but the complexity of delivering these inhibitors increases
Solution Approach 1:
The patent employs complementary RNA agents (siRNA, shRNA, ASO) that can be delivered through multiple routes (intravitreal injection, intravenous injection, oral administration) and target multiple factors (Spp1, Trem2, Tspo, STAT3) with a single agent type. This multi-functionality simplifies the delivery system while maintaining effective myeloid cell activation reduction.
Solution Approach 2:
The patent uses complementary RNA agents as intermediary molecules that mediate between the administration system and the target factors. These agents serve as deliverable carriers that can be introduced into the body and subsequently translate into functional inhibition of myeloid activating factors, reducing the complexity of direct factor delivery.
3Reliability
If SOCS3 expression is increased, then protective effect on the retina is enhanced, but the mechanism becomes more complex
Solution Approach 1:
The patent merges the inhibition of activating factors (Spp1, Trem2, Tspo, STAT3) with the enhancement of protective factor (SOCS3) into a coordinated therapeutic approach. By combining these actions through complementary RNA agents, the invention creates a synergistic effect that enhances retinal protection while managing the complexity through unified delivery mechanisms.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Reduces myeloid lineage cell activation by up to 100%, thereby decreasing retinal neovascularization and potentially preventing blindness, with minimal side effects.
Implementation Method 1
the agent comprises a small interfering RNA (siRNA), a short hairpin RNA (shRNA), or an antisense oligonucleotide (ASO) that is complementary to a gene encoding the factor associated with myeloid cell activation
Implementation Method 2
the agent comprises a viral vector that encodes a siRNA or a shRNA that is complementary to a gene encoding the factor associated with myeloid cell activation
Data Source
AI summary
Provided herein are methods for reducing the activation of myeloid lineage cells of a subject by targeting the expression and/or activity of factors that contribute to myeloid cell activation with a therapeutic agent. As a result of these methods, the activity of myeloid lineage cells that contribute to neovascularization in the retina of a subject may be reduced. The methods are useful for the treatment and/or prevention of various retinal diseases and injuries, including retinopathy of prematurity (ROP), age-related macular degeneration (AMD), retinitis pigmentosa, or diabetic retinopathy.