Source 1primary paper2026MED
Toolkit/Ra1-based Ras-p65 anchoring aptamer
Ra1-based Ras-p65 anchoring aptamer
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
As a proof of concept, we used the Ra1 aptamer targeting Ras and the DNA ligand specific for p65 or E2F1 to construct anchoring aptamers.
Usefulness & Problems
Why this is useful
This proof-of-concept anchoring aptamer combines a Ras-binding aptamer with a p65-binding DNA ligand. The abstract states that simultaneous binding induces cytoplasmic relocalization and functional inactivation of p65.; proof-of-concept relocalization of p65
Source:
This proof-of-concept anchoring aptamer combines a Ras-binding aptamer with a p65-binding DNA ligand. The abstract states that simultaneous binding induces cytoplasmic relocalization and functional inactivation of p65.
Source:
proof-of-concept relocalization of p65
Problem solved
It provides a concrete example of how the anchoring aptamer platform can redirect a disease-relevant transcription factor away from its normal nuclear activity. The reported outcome is p65 relocalization and inactivation.; links Ras membrane anchoring to p65 recruitment for relocalization
Source:
It provides a concrete example of how the anchoring aptamer platform can redirect a disease-relevant transcription factor away from its normal nuclear activity. The reported outcome is p65 relocalization and inactivation.
Source:
links Ras membrane anchoring to p65 recruitment for relocalization
Problem links
links Ras membrane anchoring to p65 recruitment for relocalization
LiteratureIt provides a concrete example of how the anchoring aptamer platform can redirect a disease-relevant transcription factor away from its normal nuclear activity. The reported outcome is p65 relocalization and inactivation.
Source:
It provides a concrete example of how the anchoring aptamer platform can redirect a disease-relevant transcription factor away from its normal nuclear activity. The reported outcome is p65 relocalization and inactivation.
Published Workflows
Objective: Engineer heterobifunctional nucleic acid constructs that relocalize transcription factors to the cytoplasm and functionally inactivate them, with therapeutic proof of concept in cancer-relevant settings.
Why it works: The workflow is based on joining one ligand that binds a plasma membrane-anchored protein with another ligand that recruits a transcription factor, so simultaneous binding can relocalize the transcription factor to the cytoplasm and reduce its function.
simultaneous binding to a plasma membrane-anchored protein and a transcription factorcytoplasmic sequestration of transcription factorsheterobifunctional aptamer designlentiviral expression
Stages
- 1.Anchoring aptamer construct design(library_design)
This stage creates the heterobifunctional constructs needed for induced relocalization.
Selection: Combine a membrane-anchor-binding ligand with a transcription-factor-binding ligand using a linker to create heterobifunctional nucleic acids.
- 2.Proof-of-concept functional testing(functional_characterization)
This stage establishes that the designed anchoring aptamers produce the intended mechanistic effect on p65 or E2F1.
Selection: Test whether simultaneous binding to Ras and the target transcription factor induces cytoplasmic relocalization and functional inactivation.
- 3.Sustained expression and tumor-growth validation(in_vivo_validation)
This stage tests whether the platform can be deployed in a sustained manner and produce an antitumor outcome.
Selection: Use lentiviral expression to test sustained p65 cytoplasmic retention and tumor growth inhibition.
Steps
- 1.Assemble heterobifunctional anchoring aptamers from anchor-binding and TF-binding ligandsengineered constructs
Create constructs capable of binding a plasma membrane-anchored protein and a transcription factor simultaneously.
Construct design is required before testing whether relocalization can occur.
- 2.Test simultaneous binding-driven relocalization and inactivation of p65 or E2F1constructs being tested
Determine whether the anchoring aptamers can relocalize and functionally inactivate target transcription factors.
Mechanistic proof of concept is needed before moving to sustained expression and tumor studies.
- 3.Deploy anchoring aptamers with lentiviral expression for sustained p65 retention and tumor-growth testingexpression/deployment system
Evaluate whether sustained expression of anchoring aptamers can maintain p65 cytoplasmic retention and inhibit tumor growth.
After proof-of-concept relocalization is established, sustained deployment is tested for therapeutic effect.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Mechanisms
bifunctional molecular tetheringfunctional inactivation by cytoplasmic sequestrationinduced subcellular relocalizationTechniques
No technique tags yet.
Target processes
localizationInput: Chemical
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: payload burdenoperating role: regulatorswitch architecture: recruitment
It requires the Ra1 Ras-targeting aptamer and a DNA ligand specific for p65, joined in an anchoring aptamer format. The abstract does not specify linker length or sequence.; requires the Ra1 aptamer targeting Ras; requires a p65-specific DNA ligand
The abstract does not show whether this exact construct works independently of Ras context or in all cell types. It also does not provide quantitative binding or localization performance.; component sequence and exact architecture are not given in the abstract; depends on Ras binding and p65-specific ligand binding
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
A lentiviral expression system of anchoring aptamers achieved sustained cytoplasmic retention of p65 and marked inhibition of tumor growth.
Using a lentiviral expression system of anchoring aptamers, we achieved sustained cytoplasmic retention of p65 and marked inhibition of tumor growth.
This work establishes anchoring aptamers as a universal platform for transcription factor relocalization.
This work establishes a universal platform for TF relocalization, offering promising opportunities for innovative anticancer therapeutic strategies.
Anchoring aptamers are heterobifunctional nucleic acids composed of two ligands joined by a linker, with one ligand targeting a plasma membrane-anchored protein and the other recruiting a transcription factor.
Anchoring aptamers are heterobifunctional nucleic acids consisting of two ligands joined by a linker: one targeting the plasma membrane-anchored protein and the other recruiting the TF.
Anchoring aptamers are a platform for relocalizing transcription factors.
We engineered anchoring aptamers as a platform for relocalizing TFs.
Ra1-based anchoring aptamers targeting Ras and either p65 or E2F1 induce cytoplasmic relocalization and functional inactivation of p65 or E2F1.
Simultaneous binding of the anchoring aptamers to Ras and either p65 or E2F1 effectively induces cytoplasmic relocalization and functional inactivation of p65 or E2F1.
Approval Evidence
1 source1 linked approval claimfirst-pass slug ra1-based-ras-p65-anchoring-aptamer
As a proof of concept, we used the Ra1 aptamer targeting Ras and the DNA ligand specific for p65 or E2F1 to construct anchoring aptamers.
Source:
proof of concept resultsupports
Ra1-based anchoring aptamers targeting Ras and either p65 or E2F1 induce cytoplasmic relocalization and functional inactivation of p65 or E2F1.
Simultaneous binding of the anchoring aptamers to Ras and either p65 or E2F1 effectively induces cytoplasmic relocalization and functional inactivation of p65 or E2F1.
Source:
Comparisons
Source-stated alternatives
The abstract contrasts this p65-targeting version with an E2F1-targeting version built on the same platform.
Source:
The abstract contrasts this p65-targeting version with an E2F1-targeting version built on the same platform.
Source-backed strengths
abstract reports effective cytoplasmic relocalization and functional inactivation
Source:
abstract reports effective cytoplasmic relocalization and functional inactivation
Compared with Opto-PIP3
Ra1-based Ras-p65 anchoring aptamer and Opto-PIP3 address a similar problem space because they share localization.
Shared frame: same top-level item type; shared target processes: localization; same primary input modality: chemical
Compared with PROTAC
Ra1-based Ras-p65 anchoring aptamer and PROTAC address a similar problem space because they share localization.
Shared frame: same top-level item type; shared target processes: localization; same primary input modality: chemical
Compared with Ra1-based Ras-E2F1 anchoring aptamer
Ra1-based Ras-p65 anchoring aptamer and Ra1-based Ras-E2F1 anchoring aptamer address a similar problem space because they share localization.
Shared frame: same top-level item type; shared target processes: localization; same primary input modality: chemical
Ranked Citations
- 1.