US 12,065,651 B2
Viral synthetic nucleic acid sequences and use thereof
Tamir Tuller, Herzelia Pituach (IL); Eli Goz, Herzliya (IL); Oriah Mioduser, Tel Aviv (IL); and Alon Diament, Tel Aviv (IL)
Assigned to SYNVACCINE LTD., Tel Aviv (IL)
Appl. No. 16/480,671
Filed by SYNVACCINE LTD., Tel-Aviv (IL)
PCT Filed Jan. 25, 2018, PCT No. PCT/IL2018/050093
§ 371(c)(1), (2) Date Jul. 24, 2019,
PCT Pub. No. WO2018/138727, PCT Pub. Date Aug. 2, 2018.
Claims priority of provisional application 62/450,115, filed on Jan. 25, 2017.
Prior Publication US 2019/0359990 A1, Nov. 28, 2019
Int. Cl. C12N 15/67 (2006.01); C12N 7/00 (2006.01); G16B 25/10 (2019.01)
CPC C12N 15/67 (2013.01) [C12N 7/00 (2013.01); G16B 25/10 (2019.02); C12N 2710/16621 (2013.01); C12N 2710/16634 (2013.01); C12N 2710/16662 (2013.01); C12N 2770/24121 (2013.01); C12N 2770/24134 (2013.01); C12N 2770/24162 (2013.01); C12N 2795/10321 (2013.01); C12N 2795/10362 (2013.01); C12N 2800/22 (2013.01); C12N 2840/10 (2013.01)] 18 Claims
 
1. A method for producing a nucleic acid molecule optimized or deoptimized for expression in a particular cellular context within a cell, the method comprising:
a. selecting a coding sequence,
b. selecting a reference set of genes expressed in a particular cellular context within a cell wherein said reference set is a subset of said cell's total genome or is a set of viral genes coordinately expressed in said cellular context and which are a subset of a virus's genome,
c. for each codon of said coding sequence, computing a parameter that effects translation rate for said codon and its synonymous codons over all sequences in the reference set, and
d. substituting at least one codon of said coding sequence with a synonymous codon with a faster rate of translation in said particular cellular context, in order to optimize said coding sequence or substituting at least one codon of said coding sequence with a synonymous codon with a slower rate of translation in said particular cellular context, in order to deoptimize said coding sequence,
thereby producing a nucleic acid molecule optimized or deoptimized for expression in a particular cellular context.