Methods and compositions to increase somatic cell nuclear transfer (SCNT) efficiency by removing histone H3-lysine trimethylation

A culture medium comprising a population of mammalian somatic cell nuclear transfer (SCNT) embryo-derived embryonic stem cells (ntESCs) isolated in vitro or ex vivo from an inner cell mass of a mammalian SCNT embryo comprising or expressing an exogenous agent that decreases H3K9me3 methylation in the mammalian SCNT embryo, wherein one or both of the ntESCs and the SCNT embryo are genetically modified, wherein the ntESCs in the culture medium are pluripotent or totipotent ntESCs and are maintained in the culture medium in a pluripotent or totipotent undifferentiated state;

• and wherein:
• (i) the agent increases the expression or activity of at least one of Kdm4a (Jmjd2a), Kdm4b (Jmjd2b), Kdm4c (Jmjd2c) or Kdm4d (Jmjd2d), or is an inhibitor of a H3K9 methyltransferase in the mammalian SCNT embryo;
• or
• (ii) the agent comprises an mRNA sequence corresponding to any one of SEQ ID NOs:
• 1-8.