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Bioengineered silkworm model for expressing human neurotrophin-4 with potential biomedical application
Wenchang Zhang1,2,3, Zhiqing Li1,2,3, Weiqun Lan1,2,3
1State Key Laboratory of Silkworm Genome Biology, Biological Science Research Center, Southwest University, Chongqing, China.
Frontiers in Physiology
|January 23, 2023
Summary
Silkworms were engineered to produce functional neurotrophin-4 (NT-4) protein in silk. This NT-4 silk material promotes nerve cell survival, differentiation, and repair, offering potential for tissue engineering and neural regeneration.
Area of Science:
- Biotechnology
- Neuroscience
- Materials Science
Background:
- Neurotrophin-4 (NT-4) is crucial for nerve cell survival, differentiation, and repair.
- Challenges exist in sourcing sufficient NT-4 protein and achieving efficient delivery.
- Silk proteins offer a biocompatible scaffold for therapeutic protein delivery.
Purpose of the Study:
- To engineer silkworms to produce functional human NT-4 protein using a silk gland bioreactor.
- To evaluate the bioactivity and biocompatibility of NT-4-functionalized silk materials.
- To explore applications in neural regeneration and tissue engineering.
Main Methods:
- Genetic engineering of silkworms to express human NT-4 in silk glands.
- Culturing mouse HT22 cells and chicken embryo dorsal root ganglion (DRG) neurons.
- Assessing cell proliferation, differentiation, migration, and neurite outgrowth using NT-4 silk materials.
- Evaluating cytotoxicity of silk materials.
Main Results:
- Successfully produced human NT-4-functionalized silk material in silkworm silk glands.
- NT-4 silk material promoted mouse HT22 cell proliferation without cytotoxicity.
- Functional silk material induced HT22 cell differentiation and enhanced DRG neurite outgrowth.
- Demonstrated high bioactivity of NT-4 produced in the silkworm model.
Conclusions:
- Silkworm-based production of NT-4 offers a scalable source of bioactive protein.
- NT-4 functionalized silk materials show promise for neural regeneration and tissue engineering.
- Further development of silk materials with NT-4 could lead to advanced therapeutic applications.

