Delayed Lagging Strand Synthesis Promotes Male Fertility during Aging

Case ID:
C18066
Disclosure Date:
9/22/2023

Inhibition-based Method for Stem Cells Induction from Non-Stem Cells 

 Value Proposition:

·      Induces stem cells from non-stem cells through modification of gene expression or function.

·      Relies on influencing a single DNA replication component rather than multiple molecular factors.

·      Successfully rescues both male and female fertility in Drosophila aging model.


Technology Description

Researchers at Johns Hopkins have developed a method to induce stem cells from non-stem cells through manipulation of a single DNA replication component for potential applications in injury and/or aging. This modulation leads to altered chromatin architecture and reverts non-stem cells to a chromatin architecture like that of stem cells. Current work demonstrates the newly de-differentiated cells can re-differentiate into functional sperm to rescue male fertility. This phenomenon has also been found in female flies. Furthermore, fine tuning of an inhibitor to modulate the activity of this DNA replication component significantly enhances the efficiency of reprogramming human embryonic fibroblasts into induced pluripotent stem cells (iPSCs).

 

Unmet Need

Loss of stem cells or their proper activities increases during aging and/or injury. Thus, regenerating stem cells poses a valuable field for research. Although it is currently possible to induce pluripotent stem cells through Yamanaka factors, the method is complex, time consuming, and has a low success rate. Furthermore, using Yamanaka factors often have a higher risk of inducing cancers. As such, there is a need for new, more elegant methods to generate stem cells under their physiological conditions.

 

Stage of Development

·      Inventors have completed a proof-of-concept study with in vivo Drosophila models.


Data Availability

Data available upon request.

 

Publication

Reduced Levels of Lagging Strand Polymerases Shape Stem Cell Chromatin

Jonathan Snedeker, Brendon E. M. Davis, Rajesh Ranjan, Matthew Wooten, Joshua Blundon, Xin Chen

bioRxiv 2024.04.26.591383; doi: https://doi.org/10.1101/2024.04.26.591383

https://biorxiv.org/cgi/content/short/2024.04.26.591383v1

Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
COMPOSITIONS AND METHODS FOR ALTERING DNA POLYMERASE α AND PRIMASE PRO: Provisional United States 63/565,742   3/15/2024     Pending
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For Information, Contact:
Heather Curran
hpretty2@jhu.edu
410-614-0300
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