Exosomes: Driving Clinically Relevant Phenotypes through Metabolic Modulation



Mitochondrial disorders are a group of clinically heterogeneous diseases, commonly defined by a lack of cellular energy. Mitochondrial DNA (mtDNA) mutations and loss of mtDNA genomes account for more then 15% of mitochondrial disorders. Increasing evidence supports the involvement of mtDNA mutations in a plethora of human pathological conditions: aging, neurodegeneration, tumorigenesis, and metabolic defects.

The horizontal transfer of the entire mtDNA and its role in rescuing metabolic proficiency has never been investigated. But investigators in MSK’s Department of Medicine/Breast Cancer Program have identified the full mitochondrial genome in circulating extracellular vesicles (EVs) from patients with hormonal-therapy (HT) resistant metastatic breast cancer. Their early-stage findings demonstrate that the horizontal transfer of mtDNA from EVs can act as an oncogenic signal, promoting an exit from metabolic dormancy and resistance to hormonal therapy in oxidative phosphorylation (OXPHOS)-dependent breast cancer.

These results show the potential to detect and diagnose mtDNA-related conditions through the analysis of extracellular vesicles such as exosomes. This novel research also supports the possibility of administering exosomes/microvesicles with healthy/functional mitochondrial DNA as a treatment to patients with mtDNA-related disorders; such therapy could functionally mediate healthy phenotypes through metabolic modulation and potentially turn compromised cells into functional ones.


  • Potential to develop as a platform technology, with a number of possible applications, including the ability to quantify mtDNA, and diagnose and study mtDNA-related disorders.

  • By exploiting exosome-mediated transfer of genetic material, this technology could facilitate the release of exogenous mtDNA genomes in the mitochondria of recipient cells, improving mitochondrial function in human mtDNA disease (mtDNA-related genetic therapies).

  • Large market: This method could improve care for patients suffering from mtDNA-related diseases including cardiac, neuromuscular, neurodegenerative, and metabolic disorders.




Application pending, filed January 2017


Pasquale Sansone, ScD, PhD, Research Associate, Laboratory of Jacqueline Bromberg, MD, PhD, Department of Medicine/Breast Cancer Program, Memorial Sloan Kettering.


Jesse Baumgartner, CFA, Licensing Manager
Tel: 646-888-1081
ail: baumgarj@mskcc.org

Stage of Development

In vitro