KIFC1/HSET Spindle Stabilization in Human Oocytes
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Solution Overview
Problem
Human oocytes exhibit unstable spindles during meiosis due to the lack of KIFC1/HSET, leading to high aneuploidy rates and genetic disorders, which existing technologies have not adequately addressed.
Innovation Solution
Introduce KIFC1/HSET protein or mRNA encoding KIFC1/HSET into human oocytes to stabilize the spindles, thereby improving spindle stability and reducing aneuploidy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If human oocytes rely on acentrosomal spindle assembly, then spindle formation occurs without centrosomes, but spindle stability deteriorates leading to pole widening and fragmentation
Solution Approach 1:
The patent introduces KIFC1/HSET as an intermediary protein that mediates between the acentrosomal spindle assembly mechanism and spindle pole stability. KIFC1/HSET localizes to spindle poles and crosslinks microtubules, providing stabilizing force without requiring centrosomes. This intermediary protein resolves the contradiction by enabling stable pole organization through an alternative mechanism.
Solution Approach 2:
The patent changes the molecular composition parameter by introducing KIFC1/HSET protein into human oocytes. This parameter change transforms the unstable acentrosomal spindle system into a stable one by adding a specific molecular component that provides pole-focusing activity and microtubule crosslinking capability.
2Stability of the object's composition
If KIFC1/HSET is introduced into human oocytes, then spindle stability improves, but device complexity increases due to additional molecular components
Solution Approach 1:
The patent employs microinjection technology to deliver KIFC1/HSET protein or mRNA into human oocytes. The oocyte's own translational machinery then synthesizes the KIFC1/HSET protein endogenously, allowing the system to self-produce the stabilizing component rather than requiring continuous external supply or complex delivery systems.
3Reliability
If KIFC1/HSET is introduced into human oocytes, then aneuploidy rate decreases, but the procedure complexity increases
Solution Approach 1:
The patent applies KIFC1/HSET introduction to human oocytes before fertilization occurs. This preliminary stabilization of the spindle apparatus ensures proper chromosome alignment and segregation during meiosis I and II, preventing aneuploidy formation in advance. The corrective action is taken before the harmful effect (aneuploidy) can manifest.
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
Stabilization of spindles in human oocytes and zygotes by introducing KIFC1/HSET, significantly reducing the risk of aneuploidy and improving assisted reproductive technology outcomes.
Implementation Method 1
KIFC1/HSET localizes to the poles of the meiotic spindle and stabilizes it by organizing the microtubules
Implementation Method 2
KIFC1/HSET is a motor protein that moves towards the minus-end of microtubules and has the ability to slide or crosslink microtubules
Implementation Method 3
KIFC1/HSET localizes to the poles of the mitotic spindle and stabilizes it by organizing the microtubules
Implementation Method 4
KIFC1/HSET is a motor protein that moves towards the minus-end of microtubules and has the ability to slide or crosslink microtubules
Data Source
Figure 1A
Figure 1B~1C
Figure 1D~1E
AI summary
It has been surprisingly found that human oocytes lack the important spindle- associated protein KIFC1/HSET. The application describes a method stabilising the human spindle with KIFC1/HSET. Specifically, the method relates to introducing (i) KIFC1/HSET protein or (ii) mRNA encoding KIFC1/HSET into a human oocyte. Furthermore, the application relates to a non-naturally occurring human oocyte, wherein a (i) KIFC1/HSET protein or (ii) KIFC1/HSET mRNA has been introduced into a naturally occurring human oocyte thereby obtaining the non-naturally occurring oocyte. Additionally, the application relates to a (i) KIFC1/HSET protein or (ii) mRNA encoding the KIFC1/HSET for use in a method of lowering the probability of having a disorganized and/or a multipolar spindle during mitosis in a human zygote by introducing the (i) KIFC1/HSET protein or (ii) mRNA encoding the KIFC1/HSET into the human zygote. Moreover, the application discloses a complex comprising (i) a KIFC1/HSET protein and (ii) a human meiotic spindle or a human mitotic spindle, wherein the KIFC1/HSET protein has been introduced into a human oocyte or zygote.