Source 1primary paper2025PPR
Toolkit/ML Int&in
ML Int&in
Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
ML Int&in is a machine learning–guided computational design method for identifying unnatural split sites in the fast split inteins gp41-1 and NrdJ-1. In the cited preprint, these designs yielded functional split intein variants with reduced fragment affinity and supported blue-light-activatable protein splicing systems that controlled Cre recombinase in mammalian cells.
Usefulness & Problems
Why this is useful
This method is useful for engineering conditional split inteins whose activity can be externally regulated while retaining productive protein splicing. In the cited study, it enabled blue light–dependent control of Cre recombinase and was further applied to spatially control apoptosis through localized expression of truncated BID and caspase-8.
Source:
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Source:
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
Problem solved
The method addresses the challenge of finding noncanonical split sites in fast split inteins that remain functional but have reduced spontaneous fragment association. This property supported construction of light-activatable intein systems for regulated protein splicing in mammalian cells.
Source:
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Source:
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
Taxonomy & Function
Primary hierarchy
Technique Branch
Method: A concrete computational method used to design, rank, or analyze an engineered system.
Mechanisms
blue light-dependent activationblue light-dependent activationreduction of mutual fragment affinityreduction of mutual fragment affinitysplit intein-mediated protein splicingsplit intein-mediated protein splicingTechniques
Computational DesignTarget processes
No target processes tagged yet.
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenoperating role: builderswitch architecture: multi componentswitch architecture: recruitmentswitch architecture: split
The method was used to design split variants of gp41-1 and NrdJ-1 for mammalian-cell protein splicing applications. The supplied evidence indicates integration into blue-light-activatable systems controlling Cre recombinase, but it does not provide construct architecture, photoreceptor components, illumination parameters, or delivery details.
The evidence provided here comes from a single 2025 preprint and summarizes applications rather than detailed benchmarking of model performance, design success rate, or failure modes. Quantitative comparisons, independent replication, and broader validation across additional inteins, cargos, or cell types are not described in the supplied evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
Light-activatable gp41-1 and NrdJ-1 inteins enabled blue light–dependent control of Cre recombinase activity in mammalian cells.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
The blue-light-controlled intein-Cre system was exploited to spatially control apoptosis via localized expression of truncated BID and caspase-8.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Reduced mutual affinity in engineered split intein fragments was harnessed to create conditional inteins by controlling fragment proximity with a light-inducible heterodimerization system.
Approval Evidence
1 source1 linked approval claimfirst-pass slug ml-int-in
Using the ML Int&in algorithm, we predicted unnatural split sites in two of the fastest and most efficient split inteins, gp41-1 and NrdJ-1, to generate functional variants with fragments of reduced mutual affinity.
Source:
engineering resultsupports
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
Source:
Comparisons
Source-backed strengths
The reported designs produced functional split variants of both gp41-1 and NrdJ-1, indicating applicability across more than one intein scaffold. The resulting systems enabled blue light–dependent regulation of Cre activity in mammalian cells and supported spatial control of apoptosis in a localized illumination context.
Source:
ML Int&in predicted unnatural split sites in gp41-1 and NrdJ-1 that generated functional split intein variants with reduced mutual fragment affinity.
Compared with free-energy calculations
ML Int&in and free-energy calculations address a similar problem space.
Shared frame: same top-level item type
Compared with mathematical model
ML Int&in and mathematical model address a similar problem space.
Shared frame: same top-level item type
Strengths here: looks easier to implement in practice.
Compared with SwiftLib
ML Int&in and SwiftLib address a similar problem space.
Shared frame: same top-level item type
Ranked Citations
- 1.