Somatic Stem Cell Gene Therapy for Infertility Without Germline Transmission
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods offer limited options for men with non-obstructive azoospermia (NOA) and women with premature ovarian insufficiency (POI) to conceive biologically, as existing treatments for these conditions are ineffective or unavailable, particularly for cases where infertility is caused by genetic mutations affecting germ cell development.
Innovation Solution
The development of gene therapy methods involving ex vivo gene therapy, where recombinant nucleic acid molecules are introduced into spermatogonial stem cells or induced pluripotent stem cells to correct genetic mutations causing NOA or POI, allowing for the transplantation of transformed cells to regenerate spermatogenesis or oogenesis, thereby producing sperm or eggs without transmitting the therapeutic gene to offspring.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If gene therapy is applied to treat NOA or POI, then the infertile phenotype is corrected, but the therapeutic gene may be transmitted to offspring
Solution Approach 1:
The patent extracts the therapeutic gene from the germline transmission pathway by applying gene therapy to somatic cells (spermatogonial stem cells or induced pluripotent stem cells) rather than germ cells. This allows the therapeutic effect to be achieved without the modified genes being passed to offspring, thus resolving the contradiction between treatment effectiveness and avoidance of harmful germline transmission.
2Adaptability or versatility
If conventional treatments are used for NOA or POI, then the treatment options are limited, but the effectiveness is poor or unavailable
Solution Approach 1:
The patent changes the fundamental parameter of treatment approach from conventional methods (which have limited effectiveness) to gene therapy involving somatic cell modification. This parameter change enables treatment of genetic mutations causing NOA or POI that were previously untreatable, significantly improving both adaptability and effectiveness.
3Reliability
If the therapeutic gene is transmitted to offspring, then the mutation is corrected in the family lineage, but the offspring inherit unwanted genetic modifications
Solution Approach 1:
The patent extracts the therapeutic correction from the heritable lineage by targeting somatic cells that do not pass genes to offspring. The corrected somatic cells can regenerate the germ line without transmitting the therapeutic gene, thus correcting the mutation effect in the patient while avoiding unwanted genetic modifications in offspring.
Data Source
AI summary
Provided are ex vivo and in vivo methods utilizing therapeutic genes for treatment of male and female infertility, including non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) and comorbid diseases, with or without transmitting the therapeutic gene to offspring of the infertile subject. Germline gene therapy methods are also described to reduce or eliminate disease from families with or without transmission of the therapeutic gene to offspring.