RNAi-based logic circuitry coupled to Cas9-mediated transcriptional control in human cells and applications to stem cell technology
Name
986497452-MIT.pdf
Description
Full printable version
Size
4.28 MB
Format
Adobe PDF
Checksum (MD5)
e8bb56bb1199ed6df01a13689faf319d
Author(s)
Palacios, Sebastian Ricardo
Advisor(s)
Ron Weiss.
Alternative Title
Ribonucleic acid interference-based logic circuitry coupled to Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9-mediated transcriptional control in human cells and applications to stem cell technology
Date Issued
2017
Publisher
Massachusetts Institute of Technology
Abstract
This work demonstrates fundamental advancements towards the construction of an RNAi-based molecular computing core genetically encoded in the genome of human induced pluripotent stem cells (hiPSCs). This architecture can be theoretically programmed to precisely control stem cell differentiation. First, we use computational biology to analyze differential miRNA expression during human stem cell differentiation and guide biological design. We then design, build, and test proof-of-concept RNAi-based circuits in living human cells and couple them to Cas9-mediated transcriptional control. Finally, we demonstrate stable integration of an RNAi-based sensor in chromosome 19 (AAVS1 locus) of hiPSCs using landing pad technology followed by successful differentiation into brain-like tissue.
Description
Thesis: S.M., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2017.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 37-38).
Subjects
Electrical Engineering and Computer Science.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Terms of Use
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