Abstract: The present invention relates to engineered polynucleotides and constructs comprising nucleic acid sequences encoding a specific splice-variant (sFLT1-14) of the VEGFR family Flt-1, methods for efficient propagation and expression thereof and compositions and uses thereof. More particularly, the invention relates to isolated polynucleotides comprising a nucleic acid sequence coding for sFlt1-14 or any fragment thereof comprising the serine-rich C-terminus region of said sFlt1-14, wherein at least one of the TCA serine coding codons in said serine-rich C-terminus region of sFlt1-14 as encoded by the nucleic acid sequence of SEQ ID NO. 1, is replaced by any one of TCT, TCC, TCG, AGT, AGC. The invention further provides compositions and method of treating VEGF-associated medical conditions using the polynucleotides of the invention.