TGFBetaR2 endonuclease variants, compositions, and methods of use
Assignee2seventy bio, Inc.
InventorsJordan Jarjour, Kyle Havens
Life of this patent
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Abstract
The present disclosure provides improved genome editing compositions and methods for editing a TGFβR2 gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.
Claims19
A polypeptide comprising an I-OnuI homing endonuclease (HE) variant that cleaves a target site in the human transforming growth factor beta receptor 2 (TGFβR2) gene, wherein the I-OnuI HE variant comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:
- 7, wherein the polypeptide binds and cleaves the polynucleotide sequence set forth in SEQ ID NO:
- 11, and wherein the I-OnuI HE variant comprises the following amino acid substitutions of SEQ ID NO:
- 4:
- (a) L26M, N32R, K34Q, S35R, S36K, V37A, G38N, 540G, E42S, G44V, Q46E, T48G, V68K, A70R, N75G, A76S, S78R, K80S, V116L, L138M, T143N, S159P, F168L, E178D, C180S, F182G, N184D, S188R, S190R, L192T, G193T, Q195G, Q197G, V199R, T203S, K207R, Y223R, K225Y, K227R, F232N, and T240R;
- or
- (b) L26M, N32R, K34Q, S35R, S36K, V37A, G38N, S40G, E42S, G44V, Q46E, T48G, V68K, A70R, N75G, A76S, S78R, K80S, V116L, L138M, T143N, S159P, F168L, E178D, C180S, F182G, N184D, S188R, S190R, L192T, G193T, Q195G, Q197G, V199R, T203S, K207R, Y223H, K225Y, K227R, F232N, T240R, and E264K.
A polynucleotide comprising a nucleotide sequence encoding a polypeptide comprising an I-OnuI homing endonuclease (HE) variant that cleaves a target site in the human transforming growth factor beta receptor 2 (TGFβR2) gene, wherein the I-OnuI HE variant comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:
- 7, wherein the polypeptide binds and cleaves the polynucleotide sequence set forth in SEQ ID NO:
- 11, and wherein the I-OnuI HE variant comprises the following amino acid substitutions of SEQ ID NO:
- 4:
- (a) L26M, N32R, K34Q, S35R, S36K, V37A, G38N, S40G, E42S, G44V, Q46E, T48G, V68K, A70R, N75G, A76S, S78R, K80S, V116L, L138M, T143N, S159P, F168L, E178D, C180S, F182G, N184D, S188R, S190R, L192T, G193T, Q195G, Q197G, V199R, T203S, K207R, Y223R, K225Y, K227R, F232N, and T240R;
- or
- (b) L26M, N32R, K34Q, S35R, S36K, V37A, G38N, S40G, E42S, G44V, Q46E, T48G, V68K, A70R, N75G, A76S, S78R, K80S, V116L, L138M, T143N, S159P, F168L, E178D, C180S, F182G, N184D, S188R, S190R, L192T, G193T, Q195G, Q197G, V199R, T203S, K207R, Y223H, K225Y, K227R, F232N, T240R, and E264K.
Dependencies are inferred from the claim text.