Toolkit/near-infrared light activatable chemically induced split-Cas9/dCas9 system

near-infrared light activatable chemically induced split-Cas9/dCas9 system

Multi-Component Switch·Research·Since 2025

Also known as: near-infrared photocleavable dimerization complex-activated split-Cas9/dCas9 system, split-Cas9/dCas9 system

Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.

Summary

The near-infrared light activatable chemically induced split-Cas9/dCas9 system is a multi-component CRISPR switch in which split Cas9 or dCas9 is activated through a near-infrared photocleavable dimerization complex. It is intended to provide near-infrared light-gated control of CRISPR genome editing-related activity.

Usefulness & Problems

Why this is useful

This system is useful because it aims to control CRISPR activity with near-infrared light rather than UV or blue light. The cited motivation is to improve tissue penetration and reduce the safety concerns associated with UV-dependent light-activatable CRISPR systems.

Source:

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.

Problem solved

It is designed to address the limitation that most light-activatable CRISPR systems require UV or blue light, which constrains tissue penetration and raises safety concerns. It also targets shortcomings of some longer-wavelength CRISPR systems that are reported to have slow activation or toxicity and biocompatibility issues in humans.

Published Workflows

Objective: Develop a light-activatable CRISPR approach that reduces off-target effects by enabling spatial and temporal control of CRISPR activation in targeted cells using near-infrared light.

Why it works: The abstract argues that off-target effects can be minimized if CRISPR is activated mainly in targeted cells, and that near-infrared activation addresses penetration and safety limitations of shorter-wavelength systems.

activation of split Cas9/dCas9 through a near-infrared photocleavable dimerization complexrestricting CRISPR activation primarily to targeted cellsnear-infrared light-triggered activationchemically induced dimerization-based controlsplit-protein CRISPR design

Taxonomy & Function

Primary hierarchy

Mechanism Branch

Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.

Techniques

No technique tags yet.

Target processes

editing

Input: Light

Implementation Constraints

The available evidence indicates a multi-component design involving split Cas9 or dCas9 and a near-infrared photocleavable dimerization complex. Specific construct architecture, chromophore or cofactor requirements, delivery method, expression system, and irradiation parameters are not described in the supplied evidence.

The provided evidence does not report quantitative performance, activation kinetics, editing efficiency, reversibility, or validation context for this specific split-Cas9/dCas9 implementation. Independent replication and breadth of biological testing are also not documented in the supplied material.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1comparative limitationsupports2025Source 1needs review

A small number of longer-wavelength CRISPR activation systems are limited by slow activation or toxicity and biocompatibility issues in humans.

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.
Claim 2comparative limitationsupports2025Source 1needs review

A small number of longer-wavelength CRISPR activation systems are limited by slow activation or toxicity and biocompatibility issues in humans.

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.
Claim 3comparative limitationsupports2025Source 1needs review

A small number of longer-wavelength CRISPR activation systems are limited by slow activation or toxicity and biocompatibility issues in humans.

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.
Claim 4comparative limitationsupports2025Source 1needs review

A small number of longer-wavelength CRISPR activation systems are limited by slow activation or toxicity and biocompatibility issues in humans.

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.
Claim 5comparative limitationsupports2025Source 1needs review

A small number of longer-wavelength CRISPR activation systems are limited by slow activation or toxicity and biocompatibility issues in humans.

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.
Claim 6comparative limitationsupports2025Source 1needs review

A small number of longer-wavelength CRISPR activation systems are limited by slow activation or toxicity and biocompatibility issues in humans.

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.
Claim 7comparative limitationsupports2025Source 1needs review

A small number of longer-wavelength CRISPR activation systems are limited by slow activation or toxicity and biocompatibility issues in humans.

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.
Claim 8comparative limitationsupports2025Source 1needs review

A small number of longer-wavelength CRISPR activation systems are limited by slow activation or toxicity and biocompatibility issues in humans.

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.
Claim 9comparative limitationsupports2025Source 1needs review

Most recently introduced light-activatable CRISPR systems require UV or blue light, which limits tissue penetration and raises safety concerns for UV light.

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.
Claim 10comparative limitationsupports2025Source 1needs review

Most recently introduced light-activatable CRISPR systems require UV or blue light, which limits tissue penetration and raises safety concerns for UV light.

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.
Claim 11comparative limitationsupports2025Source 1needs review

Most recently introduced light-activatable CRISPR systems require UV or blue light, which limits tissue penetration and raises safety concerns for UV light.

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.
Claim 12comparative limitationsupports2025Source 1needs review

Most recently introduced light-activatable CRISPR systems require UV or blue light, which limits tissue penetration and raises safety concerns for UV light.

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.
Claim 13comparative limitationsupports2025Source 1needs review

Most recently introduced light-activatable CRISPR systems require UV or blue light, which limits tissue penetration and raises safety concerns for UV light.

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.
Claim 14comparative limitationsupports2025Source 1needs review

Most recently introduced light-activatable CRISPR systems require UV or blue light, which limits tissue penetration and raises safety concerns for UV light.

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.
Claim 15comparative limitationsupports2025Source 1needs review

Most recently introduced light-activatable CRISPR systems require UV or blue light, which limits tissue penetration and raises safety concerns for UV light.

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.
Claim 16comparative limitationsupports2025Source 1needs review

Most recently introduced light-activatable CRISPR systems require UV or blue light, which limits tissue penetration and raises safety concerns for UV light.

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.
Claim 17design intentsupports2025Source 1needs review

Activating CRISPR primarily in targeted cells could minimize off-target effects by reducing unintended genetic modifications in non-target tissues.

These effects could, in principle, be minimized by ensuring that CRISPR is activated primarily in the targeted cells, thereby reducing the likelihood of unintended genetic modifications in non-target tissues.
Claim 18design intentsupports2025Source 1needs review

Activating CRISPR primarily in targeted cells could minimize off-target effects by reducing unintended genetic modifications in non-target tissues.

These effects could, in principle, be minimized by ensuring that CRISPR is activated primarily in the targeted cells, thereby reducing the likelihood of unintended genetic modifications in non-target tissues.
Claim 19design intentsupports2025Source 1needs review

Activating CRISPR primarily in targeted cells could minimize off-target effects by reducing unintended genetic modifications in non-target tissues.

These effects could, in principle, be minimized by ensuring that CRISPR is activated primarily in the targeted cells, thereby reducing the likelihood of unintended genetic modifications in non-target tissues.
Claim 20design intentsupports2025Source 1needs review

Activating CRISPR primarily in targeted cells could minimize off-target effects by reducing unintended genetic modifications in non-target tissues.

These effects could, in principle, be minimized by ensuring that CRISPR is activated primarily in the targeted cells, thereby reducing the likelihood of unintended genetic modifications in non-target tissues.
Claim 21design intentsupports2025Source 1needs review

Activating CRISPR primarily in targeted cells could minimize off-target effects by reducing unintended genetic modifications in non-target tissues.

These effects could, in principle, be minimized by ensuring that CRISPR is activated primarily in the targeted cells, thereby reducing the likelihood of unintended genetic modifications in non-target tissues.
Claim 22design intentsupports2025Source 1needs review

Activating CRISPR primarily in targeted cells could minimize off-target effects by reducing unintended genetic modifications in non-target tissues.

These effects could, in principle, be minimized by ensuring that CRISPR is activated primarily in the targeted cells, thereby reducing the likelihood of unintended genetic modifications in non-target tissues.
Claim 23design intentsupports2025Source 1needs review

Activating CRISPR primarily in targeted cells could minimize off-target effects by reducing unintended genetic modifications in non-target tissues.

These effects could, in principle, be minimized by ensuring that CRISPR is activated primarily in the targeted cells, thereby reducing the likelihood of unintended genetic modifications in non-target tissues.
Claim 24design intentsupports2025Source 1needs review

Activating CRISPR primarily in targeted cells could minimize off-target effects by reducing unintended genetic modifications in non-target tissues.

These effects could, in principle, be minimized by ensuring that CRISPR is activated primarily in the targeted cells, thereby reducing the likelihood of unintended genetic modifications in non-target tissues.
Claim 25performance claimsupports2025Source 1needs review

The photoactivation method is described as safely usable in humans in vivo, easily adaptable to different split-Cas9/dCas9 systems, and capable of rapid spatially precise light activation across various cell types.

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.
Claim 26performance claimsupports2025Source 1needs review

The photoactivation method is described as safely usable in humans in vivo, easily adaptable to different split-Cas9/dCas9 systems, and capable of rapid spatially precise light activation across various cell types.

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.
Claim 27performance claimsupports2025Source 1needs review

The photoactivation method is described as safely usable in humans in vivo, easily adaptable to different split-Cas9/dCas9 systems, and capable of rapid spatially precise light activation across various cell types.

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.
Claim 28performance claimsupports2025Source 1needs review

The photoactivation method is described as safely usable in humans in vivo, easily adaptable to different split-Cas9/dCas9 systems, and capable of rapid spatially precise light activation across various cell types.

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.
Claim 29performance claimsupports2025Source 1needs review

The photoactivation method is described as safely usable in humans in vivo, easily adaptable to different split-Cas9/dCas9 systems, and capable of rapid spatially precise light activation across various cell types.

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.
Claim 30performance claimsupports2025Source 1needs review

The photoactivation method is described as safely usable in humans in vivo, easily adaptable to different split-Cas9/dCas9 systems, and capable of rapid spatially precise light activation across various cell types.

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.
Claim 31performance claimsupports2025Source 1needs review

The photoactivation method is described as safely usable in humans in vivo, easily adaptable to different split-Cas9/dCas9 systems, and capable of rapid spatially precise light activation across various cell types.

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.
Claim 32performance claimsupports2025Source 1needs review

The photoactivation method is described as safely usable in humans in vivo, easily adaptable to different split-Cas9/dCas9 systems, and capable of rapid spatially precise light activation across various cell types.

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.
Claim 33tool descriptionsupports2025Source 1needs review

The paper reports a split-Cas9/dCas9 system activated through a near-infrared photocleavable dimerization complex.

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.
Claim 34tool descriptionsupports2025Source 1needs review

The paper reports a split-Cas9/dCas9 system activated through a near-infrared photocleavable dimerization complex.

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.
Claim 35tool descriptionsupports2025Source 1needs review

The paper reports a split-Cas9/dCas9 system activated through a near-infrared photocleavable dimerization complex.

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.
Claim 36tool descriptionsupports2025Source 1needs review

The paper reports a split-Cas9/dCas9 system activated through a near-infrared photocleavable dimerization complex.

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.
Claim 37tool descriptionsupports2025Source 1needs review

The paper reports a split-Cas9/dCas9 system activated through a near-infrared photocleavable dimerization complex.

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.
Claim 38tool descriptionsupports2025Source 1needs review

The paper reports a split-Cas9/dCas9 system activated through a near-infrared photocleavable dimerization complex.

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.
Claim 39tool descriptionsupports2025Source 1needs review

The paper reports a split-Cas9/dCas9 system activated through a near-infrared photocleavable dimerization complex.

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.
Claim 40tool descriptionsupports2025Source 1needs review

The paper reports a split-Cas9/dCas9 system activated through a near-infrared photocleavable dimerization complex.

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.

Approval Evidence

1 source5 linked approval claimsfirst-pass slug near-infrared-light-activatable-chemically-induced-split-cas9-dcas9-system
To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.

Source:

comparative limitationsupports

A small number of longer-wavelength CRISPR activation systems are limited by slow activation or toxicity and biocompatibility issues in humans.

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.

Source:

comparative limitationsupports

Most recently introduced light-activatable CRISPR systems require UV or blue light, which limits tissue penetration and raises safety concerns for UV light.

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.

Source:

design intentsupports

Activating CRISPR primarily in targeted cells could minimize off-target effects by reducing unintended genetic modifications in non-target tissues.

These effects could, in principle, be minimized by ensuring that CRISPR is activated primarily in the targeted cells, thereby reducing the likelihood of unintended genetic modifications in non-target tissues.

Source:

performance claimsupports

The photoactivation method is described as safely usable in humans in vivo, easily adaptable to different split-Cas9/dCas9 systems, and capable of rapid spatially precise light activation across various cell types.

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.

Source:

tool descriptionsupports

The paper reports a split-Cas9/dCas9 system activated through a near-infrared photocleavable dimerization complex.

To address this, we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex.

Source:

Comparisons

Source-backed strengths

The main stated strength is the use of near-infrared input in a chemically induced split-Cas9/dCas9 architecture. Based on the source claims, this design is positioned to address wavelength-related penetration and safety limitations seen in prior UV-, blue-, or some longer-wavelength CRISPR activation systems.

Source:

A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans.

Source:

A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure, severely limiting the penetration depth of light in tissue at which CRISPR can be activated, and, in the case of UV light, raising safety concerns.

Source:

This photoactivation method can be safely used in humans in vivo, easily adapted to different split-Cas9/dCas9 systems, and enables rapid, spatially precise light activation across various cell types.

Ranked Citations

  1. 1.

    Extracted from this source document.