Galpha12 Galpha13 Antisense Oligonucleotides for Angiogenesis Control
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Solution Overview
Problem
Current therapies for angiogenesis-associated conditions, such as cancer and ocular disorders, face challenges due to toxicities and acquired resistance, highlighting the need for novel strategies to modulate angiogenesis effectively.
Innovation Solution
The development of angiogenesis-modulating agents that target the α subunit of heterotrimeric GDP/GTP-binding proteins, specifically Gα12 and Gα13, by reducing or increasing their expression and activity using oligonucleotides, guanine nucleotide analogues, and antibodies to modulate angiogenesis in mammals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-angiogenesis therapies are used to treat cancer and ocular disorders, then tumor growth and abnormal angiogenesis are inhibited, but toxicities and acquired resistance occur
Solution Approach 1:
The patent extracts and targets specific G proteins (Gα12 and Gα13) as the molecular basis of angiogenesis, separating this specific target from the general angiogenesis pathway. By using antisense oligonucleotides that specifically hybridize to Gα12 and Gα13 mRNA, the therapy selectively inhibits only these particular G proteins while sparing other cellular processes, thereby reducing toxicities and acquired resistance associated with broader anti-angiogenesis therapies
Solution Approach 2:
The patent introduces antisense oligonucleotides as intermediary molecules that mediate between the administered therapeutic agent and the target Gα12/Gα13 proteins. These oligonucleotides serve as a bridge that specifically binds to and inhibits the translation of Gα12 and Gα13 mRNA into functional proteins, providing a mechanism to selectively block angiogenesis signaling without directly exposing cells to toxic small molecule inhibitors
2Reliability
If Gα12 and Gα13 expression is reduced to inhibit angiogenesis, then tumor growth is suppressed, but normal blood vessel formation may be impaired
Solution Approach 1:
The patent applies local quality by targeting Gα12 and Gα13 specifically in tumor tissues and tumor-associated vasculature, where these G proteins are overexpressed and drive pathological angiogenesis. The antisense oligonucleotides are designed to bind specifically to Gα12 and Gα13 mRNA sequences that are highly expressed in tumor contexts, thereby selectively inhibiting angiogenesis in the tumor microenvironment while preserving normal angiogenesis in healthy tissues
Solution Approach 2:
The patent employs partial action by using antisense oligonucleotides that reduce but do not completely eliminate Gα12 and Gα13 expression. This partial inhibition is sufficient to suppress tumor growth and abnormal angiogenesis while maintaining enough G protein function to support essential physiological processes and normal blood vessel formation in non-pathological tissues
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
This approach effectively reduces tumor growth and angiogenesis by decreasing Gα12 or Gα13 activity, while promoting angiogenesis by increasing their expression, offering a therapeutic benefit for various conditions associated with abnormal angiogenesis.
Implementation Method 1
an oligonucleotide that is capable of hybridizing to a nucleic acid encoding a Gα12 or Gα13 polypeptide under intracellular conditions and reducing expression of the nucleic acid in a cell
Data Source
AI summary
The invention provides an agent that reduces the expression of Gα12 or Gα13 polypeptide, as well as an agent that enhances G protein Gα12 or Gα13 expression and/or activity. An agent of the invention may be used to decrease or increase G protein Gα12 or Gα13 expression and/or activity thereby to treat or prevent the onset of a disease or condition associated with Gα12 or Gα13 expression and/or activity. The invention also provides a method for screening for an anti-cancer or anti-angiogenesis agent, as well as an agent that promotes angiogenesis.