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Universal donor stem cells and related methods

A stem cell, cell technology, applied in universal donor stem cells and related fields, can solve problems such as hindering widespread use

Pending Publication Date: 2022-01-07
PRESIDENT & FELLOWS OF HARVARD COLLEGE 17 Q
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, multiple limitations (de Rham and Villard, 2014; Tapia and Scholer, 2016) have hindered the widespread use of these methods and underscore the need for "off-the-shelf" cell products that can be easily administered to any patient in need

Method used

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  • Universal donor stem cells and related methods
  • Universal donor stem cells and related methods
  • Universal donor stem cells and related methods

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Embodiment Construction

[0050] The invention disclosed herein employs genome editing technology (e.g., CRISPR / Cas or TALEN systems) to reduce or eliminate the expression of key immune genes, or in some cases, insert tolerance-inducing factors in stem cells, making them and The prepared differentiated cells have low immunogenicity and are not susceptible to immune rejection by the subject transplanted with such cells.

[0051] As used herein for purposes of characterizing cells, the term "low immunogenicity" generally means that such cells are not susceptible to immune rejection by a subject transplanted with such cells. For example, the propensity of such poorly immunogenic cells to be immune-rejected by a subject transplanted with such cells may be reduced by about 2.5%, 5%, 10%, 20%, 30%, 40%, relative to unaltered wild-type cells. %, 50%, 60%, 70%, 80%, 90%, 95%, 97.5%, 99% or more. In some aspects, genome editing technologies (eg, CRISPR / Cas or TALEN systems) are used to modulate (eg, reduce or ...

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Abstract

Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein have modulated expression of one or more MHC-I and MHC-II human leukocyte antigens and one or more tolerogenic factors.

Description

[0001] Cross References to Related Applications [0002] This application is a continuation of U.S. Application No. 16 / 596,697, filed October 8, 2019, which is a continuation of U.S. Application No. 16 / 277,913, filed February 15, 2019, which No. 16 / 277,913 claims the benefit of U.S. Provisional Application No. 62 / 631,393, filed February 15, 2018. The entire teachings of the above applications are incorporated herein by reference. [0003] Background of the invention [0004] Therapies using human pluripotent stem cell-derived cells for transplantation have the potential to revolutionize the way disease is treated. A major obstacle to their clinical translation is the rejection of allogeneic cells by the recipient's immune system. Strategies aimed at overcoming this immune barrier include banking cells with defined HLA haplotypes (Nakajima et al., 2007; Taylor et al., 2005) and generating patient-specific induced pluripotent stem cells (iPSCs) (Takahashi et al., 2007; Yu et a...

Claims

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Application Information

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IPC IPC(8): C07K14/74C07K14/705C12N5/074C12N5/0735
CPCC12N15/1138C12N2310/20C12N5/0606C12N2502/1114C12N2501/599A61K2035/122C12N15/102C12N2510/00
Inventor 托斯滕·B·迈斯纳罗纳尔多·M·r·费雷拉杰克·L·施特罗明格沙达·A·考恩
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE 17 Q