Toolkit/macrophage transient horizontal gene transfer

macrophage transient horizontal gene transfer

Delivery Strategy·Research·Since 2019

Also known as: macrophages as a drug carrier, macrophage transient horizontal gene transfer

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

Summary

Macrophage transient horizontal gene transfer is a cell-based siRNA delivery harness in which macrophages loaded with siRNA lipoplexes transfer siRNA to cancer cells during in vitro coculture. In the reported system, transferred CIB1-siRNA reduced tumorsphere growth and lowered CIB1 and KI67 mRNA expression in MDA-MB-468 human breast cancer cells.

Usefulness & Problems

Why this is useful

This system is useful as a macrophage-mediated route for delivering siRNA cargo to cancer cells without direct transfection of the target cells. The reported study shows that transfer magnitude depends on siRNA loading and macrophage number, providing tunable control over intercellular delivery in coculture.

Source:

Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Source:

Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells.

Problem solved

It addresses the problem of moving siRNA from a carrier cell population into cancer cells in vitro and achieving functional gene knockdown after transfer. The demonstrated application was delivery of CIB1-siRNA to MDA-MB-468 breast cancer cells, with associated reduction in tumorsphere growth and target-associated mRNA readouts.

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.

Techniques

No technique tags yet.

Target processes

recombination

Implementation Constraints

The reported implementation uses macrophages as carrier cells loaded with siRNA lipoplexes and then delivered into coculture with cancer cells. Practical performance depends on the amount of siRNA loaded into macrophages and the total number of macrophages used, and functional validation was reported in MDA-MB-468 tumorsphere and mRNA knockdown assays.

The evidence provided is limited to a single 2019 study and in vitro coculture experiments. The supplied evidence does not establish in vivo performance, generality across tumor types or siRNA cargos, or detailed transfer mechanism beyond macrophage-mediated intercellular cargo transfer.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1capabilitysupports2019Source 1needs review

Macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.
Claim 2capabilitysupports2019Source 1needs review

Macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.
Claim 3capabilitysupports2019Source 1needs review

Macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.
Claim 4capabilitysupports2019Source 1needs review

Macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.
Claim 5capabilitysupports2019Source 1needs review

Macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.
Claim 6capabilitysupports2019Source 1needs review

Macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.
Claim 7capabilitysupports2019Source 1needs review

Macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.
Claim 8dose dependencesupports2019Source 1needs review

The amount of siRNA transfer depends on the amount of siRNA loaded and the total number of macrophages delivered.

The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered.
Claim 9dose dependencesupports2019Source 1needs review

The amount of siRNA transfer depends on the amount of siRNA loaded and the total number of macrophages delivered.

The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered.
Claim 10dose dependencesupports2019Source 1needs review

The amount of siRNA transfer depends on the amount of siRNA loaded and the total number of macrophages delivered.

The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered.
Claim 11dose dependencesupports2019Source 1needs review

The amount of siRNA transfer depends on the amount of siRNA loaded and the total number of macrophages delivered.

The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered.
Claim 12dose dependencesupports2019Source 1needs review

The amount of siRNA transfer depends on the amount of siRNA loaded and the total number of macrophages delivered.

The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered.
Claim 13dose dependencesupports2019Source 1needs review

The amount of siRNA transfer depends on the amount of siRNA loaded and the total number of macrophages delivered.

The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered.
Claim 14dose dependencesupports2019Source 1needs review

The amount of siRNA transfer depends on the amount of siRNA loaded and the total number of macrophages delivered.

The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered.
Claim 15functional effectsupports2019Source 1needs review

Macrophages loaded with CIB1-siRNA decrease tumorsphere growth and decrease CIB1 and KI67 mRNA expression in MDA-MB-468 human breast cancer cells.

Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells.
Claim 16functional effectsupports2019Source 1needs review

Macrophages loaded with CIB1-siRNA decrease tumorsphere growth and decrease CIB1 and KI67 mRNA expression in MDA-MB-468 human breast cancer cells.

Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells.
Claim 17functional effectsupports2019Source 1needs review

Macrophages loaded with CIB1-siRNA decrease tumorsphere growth and decrease CIB1 and KI67 mRNA expression in MDA-MB-468 human breast cancer cells.

Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells.
Claim 18functional effectsupports2019Source 1needs review

Macrophages loaded with CIB1-siRNA decrease tumorsphere growth and decrease CIB1 and KI67 mRNA expression in MDA-MB-468 human breast cancer cells.

Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells.
Claim 19functional effectsupports2019Source 1needs review

Macrophages loaded with CIB1-siRNA decrease tumorsphere growth and decrease CIB1 and KI67 mRNA expression in MDA-MB-468 human breast cancer cells.

Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells.
Claim 20functional effectsupports2019Source 1needs review

Macrophages loaded with CIB1-siRNA decrease tumorsphere growth and decrease CIB1 and KI67 mRNA expression in MDA-MB-468 human breast cancer cells.

Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells.
Claim 21functional effectsupports2019Source 1needs review

Macrophages loaded with CIB1-siRNA decrease tumorsphere growth and decrease CIB1 and KI67 mRNA expression in MDA-MB-468 human breast cancer cells.

Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells.
Claim 22modulationsupports2019Source 1needs review

Macrophage activation and Rab27a modulate the macrophage-mediated siRNA transfer process.

Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a.
Claim 23modulationsupports2019Source 1needs review

Macrophage activation and Rab27a modulate the macrophage-mediated siRNA transfer process.

Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a.
Claim 24modulationsupports2019Source 1needs review

Macrophage activation and Rab27a modulate the macrophage-mediated siRNA transfer process.

Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a.
Claim 25modulationsupports2019Source 1needs review

Macrophage activation and Rab27a modulate the macrophage-mediated siRNA transfer process.

Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a.
Claim 26modulationsupports2019Source 1needs review

Macrophage activation and Rab27a modulate the macrophage-mediated siRNA transfer process.

Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a.
Claim 27modulationsupports2019Source 1needs review

Macrophage activation and Rab27a modulate the macrophage-mediated siRNA transfer process.

Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a.
Claim 28modulationsupports2019Source 1needs review

Macrophage activation and Rab27a modulate the macrophage-mediated siRNA transfer process.

Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a.
Claim 29tumor localizationsupports2019Source 1needs review

Adoptively transferred macrophages transfected with CIB1-siRNA localize to orthotopic MDA-MB-468 tumor.

Adoptive transfer of macrophages transfected with CIB1-siRNA localizes to the orthotopic MDA-MB-468 tumor.
Claim 30tumor localizationsupports2019Source 1needs review

Adoptively transferred macrophages transfected with CIB1-siRNA localize to orthotopic MDA-MB-468 tumor.

Adoptive transfer of macrophages transfected with CIB1-siRNA localizes to the orthotopic MDA-MB-468 tumor.
Claim 31tumor localizationsupports2019Source 1needs review

Adoptively transferred macrophages transfected with CIB1-siRNA localize to orthotopic MDA-MB-468 tumor.

Adoptive transfer of macrophages transfected with CIB1-siRNA localizes to the orthotopic MDA-MB-468 tumor.
Claim 32tumor localizationsupports2019Source 1needs review

Adoptively transferred macrophages transfected with CIB1-siRNA localize to orthotopic MDA-MB-468 tumor.

Adoptive transfer of macrophages transfected with CIB1-siRNA localizes to the orthotopic MDA-MB-468 tumor.
Claim 33tumor localizationsupports2019Source 1needs review

Adoptively transferred macrophages transfected with CIB1-siRNA localize to orthotopic MDA-MB-468 tumor.

Adoptive transfer of macrophages transfected with CIB1-siRNA localizes to the orthotopic MDA-MB-468 tumor.
Claim 34tumor localizationsupports2019Source 1needs review

Adoptively transferred macrophages transfected with CIB1-siRNA localize to orthotopic MDA-MB-468 tumor.

Adoptive transfer of macrophages transfected with CIB1-siRNA localizes to the orthotopic MDA-MB-468 tumor.
Claim 35tumor localizationsupports2019Source 1needs review

Adoptively transferred macrophages transfected with CIB1-siRNA localize to orthotopic MDA-MB-468 tumor.

Adoptive transfer of macrophages transfected with CIB1-siRNA localizes to the orthotopic MDA-MB-468 tumor.

Approval Evidence

1 source5 linked approval claimsfirst-pass slug macrophage-transient-horizontal-gene-transfer
Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer

Source:

capabilitysupports

Macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture.

Source:

dose dependencesupports

The amount of siRNA transfer depends on the amount of siRNA loaded and the total number of macrophages delivered.

The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered.

Source:

functional effectsupports

Macrophages loaded with CIB1-siRNA decrease tumorsphere growth and decrease CIB1 and KI67 mRNA expression in MDA-MB-468 human breast cancer cells.

Macrophages loaded with calcium integrin binding protein-1 (CIB1)-siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA-MB-468 human breast cancer cells.

Source:

modulationsupports

Macrophage activation and Rab27a modulate the macrophage-mediated siRNA transfer process.

Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a.

Source:

tumor localizationsupports

Adoptively transferred macrophages transfected with CIB1-siRNA localize to orthotopic MDA-MB-468 tumor.

Adoptive transfer of macrophages transfected with CIB1-siRNA localizes to the orthotopic MDA-MB-468 tumor.

Source:

Comparisons

Source-backed strengths

The key strength is demonstrated horizontal transfer of siRNA from macrophages to cancer cells during coculture with measurable dose dependence on siRNA load and macrophage input. Functional activity was supported by decreased tumorsphere growth and reduced CIB1 and KI67 mRNA expression in MDA-MB-468 cells after macrophage loading with CIB1-siRNA.

Ranked Citations

  1. 1.
    StructuralSource 1Advanced Science2019Claim 1Claim 2Claim 3

    Extracted from this source document.