Source 1review2022Frontiers in Genome Editing
Toolkit/ex vivo stem cell modification and re-transplantation
ex vivo stem cell modification and re-transplantation
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Ex vivo stem cell modification and re-transplantation is a clinical delivery workflow in which a patient's own stem cells are isolated, genetically modified outside the body with CRISPR-based approaches, and returned to the same patient. The supplied evidence identifies this format as common among current clinical CRISPR trials.
Usefulness & Problems
Why this is useful
This workflow is useful because it provides a clinically used route for applying CRISPR editing to patient-derived stem cells before re-transplantation. The evidence also indicates that this setting can incorporate sequencing-based genomic surveillance to detect CRISPR-associated genomic effects, including low-frequency large-scale events.
Problem solved
It addresses the delivery and handling problem of how to perform CRISPR modification in a patient's own stem cells within a clinical workflow. The evidence further highlights an associated problem that current workflows inadequately detect large-scale aberrations such as translocations, inversions, deletions, and chromothripsis.
Problem links
We Can’t Safely and Controllably Deliver Complex Molecular Payloads to the Targets We Want in the Body
Gap mapView gapThis is a concrete delivery strategy that can reduce some in-vivo targeting and safety problems by moving payload introduction outside the body and returning modified cells afterward. It plausibly addresses part of the gap for cell therapies, though it does not solve direct in-vivo delivery to hard-to-reach tissues such as brain.
For complex organisms, ex vivo modification of stem cells provides a practical delivery and testing route when direct whole-organism programming is difficult. It could support controlled engineering of developmental potential in patient-derived or model stem cells before reintroduction.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A delivery strategy grouped with the mechanism branch because it determines how a system is instantiated and deployed in context.
Mechanisms
autologous cell re-transplantationautologous cell re-transplantationex vivo cell manipulationex vivo cell manipulationgenome editinggenome editingTechniques
No technique tags yet.
Target processes
editingImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: externally suppliedimplementation constraint: context specific validationoperating role: delivery
The documented workflow consists of ex vivo isolation of a patient's own stem cells, genetic modification, and re-transplantation, consistent with an autologous format. Sequencing-based genomic surveillance is suggested as a practical addition for detecting large-scale CRISPR-associated genomic effects, but the evidence does not specify particular sequencing platforms or assay designs.
Current workflows have difficulty detecting large-scale genomic aberrations, including translocations, inversions, deletions, and chromothripsis. The supplied evidence does not provide quantitative performance data, specific stem cell types, editing reagents, or clinical outcome metrics.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Large-scale aberrations such as translocations, inversions, deletions, and chromothripsis are more difficult to detect using current workflows, indicating a major unmet need.
However, large-scale aberrations have recently been reported such as translocations, inversions, deletions, and even chromothripsis. These are more difficult to detect using current workflows indicating a major unmet need in the field.
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Sequencing-based solutions may be able to detect large-scale CRISPR-associated genomic effects even at low frequencies of occurrence.
we summarize potential sequencing-based solutions that may be able to detect these large-scale effects even at low frequencies of occurrence
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Approval Evidence
1 source1 linked approval claimfirst-pass slug ex-vivo-stem-cell-modification-and-re-transplantation
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Source:
workflow contextsupports
Many current clinical CRISPR trials use an ex vivo workflow involving stem cell isolation, modification, and re-transplantation.
many of the current clinical trials using CRISPR involve ex vivo isolation of a patient's own stem cells, modification, and re-transplantation
Source:
Comparisons
Source-backed strengths
The main strength supported by the evidence is that this is already a common workflow in current clinical CRISPR trials, indicating practical clinical relevance. Sequencing-based approaches are also noted as a potential way to detect large-scale CRISPR-associated genomic effects even when they occur at low frequency.
Compared with cell membrane biomimetic core-shell system
ex vivo stem cell modification and re-transplantation and cell membrane biomimetic core-shell system address a similar problem space because they share editing.
Shared frame: same top-level item type; shared target processes: editing
Strengths here: looks easier to implement in practice.
Compared with delivery system
ex vivo stem cell modification and re-transplantation and delivery system address a similar problem space because they share editing.
Shared frame: same top-level item type; shared target processes: editing
Compared with oncolytic viruses
ex vivo stem cell modification and re-transplantation and oncolytic viruses address a similar problem space because they share editing.
Shared frame: same top-level item type; shared target processes: editing; shared mechanisms: genome editing
Ranked Citations
- 1.