Avian Telomerase Reverse Transcriptase for Anatidae Cell Immortalization
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Solution Overview
Problem
There is a need for a Telomerase Reverse Transcriptase that can immortalize avian cells, particularly Anatidae cells, as existing human TERT is incompatible with avian telomere maintenance apparatus, limiting the production of complex glycosylated proteins in biotechnology and viral vaccine manufacturing.
Innovation Solution
Development of a recombinant polypeptide with at least 60% amino acid sequence identity to a specific TERT sequence, capable of immortalizing Anatidae cells, using a vector with homologous sequences for site-specific insertion into the HPRT gene, and selection markers for marker elimination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If human TERT is used for cell immortalization, then cell lifespan is extended, but it is incompatible with avian telomere maintenance apparatus
Solution Approach 1:
The patent applies local quality by making the TERT protein species-specific. Instead of using universal human TERT, the invention uses avian-derived TERT sequences (from chicken, duck, goose, or turkey) that are locally adapted to work with avian telomere maintenance apparatus. This ensures compatibility at the molecular level while achieving the desired cell immortalization effect in avian cells.
2Ease of manufacture
If avian cell lines are developed for biotechnology production, then complex glycosylated proteins can be produced, but existing TERT cannot immortalize these cells
Solution Approach 1:
The patent applies self-service by using avian TERT sequences that naturally serve avian cells. The TERT protein derived from avian sources (chicken, duck, goose, or turkey) is specifically adapted to work with avian telomerase RNA and maintenance apparatus, enabling self-sustaining immortalization of avian cell lines without requiring human TERT adaptation.
3Productivity
If TERT activity is upregulated in transformed cells, then cell proliferation increases, but it leads to chromosomal instability
Solution Approach 1:
The patent applies parameter changes by modifying the TERT protein sequence to match avian species-specific parameters. By using TERT sequences with at least 60% identity to avian TERT (and preferably higher identity), the invention optimizes the protein's interaction parameters with avian telomere maintenance apparatus, achieving stable telomere maintenance that supports controlled proliferation without chromosomal instability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The recombinant TERT enables the immortalization of Anatidae cells, facilitating the production of complex proteins and viral vaccines by extending cellular lifespan and maintaining genome stability.
Implementation Method 1
telomerase reverse transcriptase, which is a nucleoprotein having a reverse transcriptase enzymatic activity. Telomerase reverse transcriptase is capable to lengthen the telomere repeat array
Data Source
AI summary
The present invention notably relates to novel recombinant telomerase reverse transcriptases, nucleic acid molecules coding them, cells comprising said nucleic acid molecule and use of these cells for the production of substance of interest.