Abstract: The present disclosure provides technologies for achieving treatment of cancer. The present disclosure provides methods and compositions for the treatment of cancer using oncoselective construct designs that can be used to encode payloads of high therapeutic interest. The present disclosure recognizes that treatment of individuals suffering from cancer with engineered nucleic acids of the disclosure in combination with immune checkpoint therapy provides unique advantages.

Abstract: The present disclosure provides technologies for achieving oncoselective translation. The use of two complementary pipelines to study the translation landscapes of cancer vs. normal cells described in this disclosure enables identification of oncoselective sequence motifs that can be used to engineer synthetic DNAs or mRNA constructs for cancer cell specific protein expression. The present disclosure describes the features of oncoselective motifs and provides embodiments of modular oncoselective construct designs that can be used to encode payloads of high therapeutic interest.

Abstract: The present disclosure provides, among other things, methods and compositions useful for induction of cell death. The present disclosure provides translatable nucleic acids encoding constitutively active payloads capable of inducing cell death. Payloads of the present disclosure are particularly useful in induction of immunogenic cell death.

Abstract: Present disclosure is directed to methods of lowering immunogenicity in long polynucleotide sequences by precise sequence engineering of immunogenic motifs in the polynucleotide sequences. This disclosure is further directed to precisely sequence engineered polynucleotides with improved functionality, such as displaying low innate immunogenicity, improved stability or high protein expression. In these polynucleotides, immunogenic sequence motifs are removed while conserving the remainder of the sequence. Compared to overall nucleotide alterations, this targeted engineering approach has unique advantages, including less disruption of the natural or optimized polynucleotide sequence, and hence, preservation of high expressivity while enabling stealthiness vis-à-vis the innate immune receptors.