Vgll4-Ucp1 Cis-Regulatory Construct for Brown Fat Activation
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Solution Overview
Problem
Current compositions and methods for increasing brown adipose tissue (BAT) are lacking, hindering effective treatment of obesity and related pathologies such as diabetes and liver disease.
Innovation Solution
A polynucleotide construct containing a cis-regulatory element and nucleotide sequence encoding a vestigial like 4 protein (Vgll4) is used, specifically promoting BAT expression through an uncoupling protein 1 (Ucp1) enhancer and promoter, with optional amino acid substitutions in TDU domains, delivered via a viral vector.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to treat obesity, then weight loss may be achieved, but effective pharmacological therapies are lacking and cannot adequately address the root cause of obesity
Solution Approach 1:
The invention changes the fundamental parameter of treatment approach by targeting BAT activation and WAT browning rather than simple caloric restriction or appetite suppression. This involves modifying the biological state of adipose tissue through specific protein expression (Vgll4) to transform tissue function and composition, thereby achieving more reliable and versatile obesity treatment
2Use of energy by moving object
If BAT is activated to burn triglycerides and glucose, then energy homeostasis is improved, but compositions and methods for increasing BAT are currently lacking
Solution Approach 1:
The invention introduces Vgll4 protein and its encoding polynucleotides as intermediary agents to mediate BAT activation and WAT browning. These intermediaries serve as the missing link between current pharmacological capabilities and desired BAT increase, enabling caloric utilization improvement through available molecular biology tools and viral vector delivery systems
3Quantity of substance
If the balance between BAT and WAT is shifted toward BAT, then obesity is reduced, but current methods cannot effectively increase BAT volume
Solution Approach 1:
The invention performs preliminary action by delivering Vgll4 encoding sequences to adipose tissue before significant obesity development or tissue transformation occurs. This proactive approach establishes the molecular machinery needed for BAT activation and WAT browning in advance, enabling more effective and faster BAT volume increase compared to reactive treatments
Data Source
AI summary
Provided is a polynucleotide, including a cis-regulatory element and a nucleotide sequence encoding a vestigial like 4 protein, wherein the cis-regulatory element includes an uncoupling protein 1 enhancer and an uncoupling protein 1 promoter. Also provided is a viral vector including said polynucleotide. Also provided is a method of transfecting a cell or a subject with said polynucleotide or said viral vector.