RNA based drugs are emerging modalities with high therapeutic potential to address the targets that are intractable by antibodies or small molecule inhibitors, along with high specificity and great flexibility in reconstructing the diseased human genome. Recent advances in programmable RNA therapies broaden the scope of RNA therapeutics, however low uptake efficiency and high toxicity of RNA counterparts (i.e. delivery vehicles) confined its use in clinics. Thus more safe and effective strategies are warranted for the efficient delivery of RNA based molecules. Here, we define and validate a new strategy to harness large-scale amounts of extracellular vesicles (RBCEVs) from readily available donor’s red blood cell units. We further showed that these extracellular vesicles are highly capable of delivering a variety of RNA molecules, including antisense oligonucleotides (ASO), Cas9 mRNA and guide RNA. Delivery of RNA drug with RBCEVs showed highly robust microRNA inhibition and precise manipulation of the genome by CRISPR-Cas-9 mediated gene editing in both adherent and non-adherent human cell line models. Moreover, local or systemic delivery of ASO-loaded RBCEVs provided efficient knockdown of the oncogenic miR-125b and suppression of breast cancer or leukemia growth in xenograft mouse models, with no evidence of cytotoxicity. For an idealistic clinical approach, human RBCEVs can easily be purified from readily available RBC units and even from patients own blood to treat the underlying diseases. Furthermore, use of RBCEVs cutoff the risk of horizontal gene transfer as they lack DNA content and thereby providing a desirable platform for the delivery of RNA molecules in the future clinical applications.