Exhibit 5.1 Chadwick L. Mills +1 650 843 5654 cmills@cooley.com Cooley LLP 3 Embarcadero Center 20th Floor San Francisco, CA 94111-4004 t: (415) 693-2000 f: (415) 693-2222 cooley.com December 23, 2022 Sangamo Therapeutics, Inc. 7000 Marina Blvd. Brisbane, California 94005 Ladies and Gentlemen: We have acted as counsel to Sangamo Therapeutics, Inc., a Delaware corporation (the “Company”), in connection with the sale of shares of its common stock, par value $0.01 per share (the “Common Stock”), having an aggregate offering price of up to $175.0 million (the “Shares”) pursuant to the Registration Statement on Form S-3 (File No. 333-255792) (the “Registration Statement”) filed with the Securities and Exchange Commission (the “Commission”) under the Securities Act of 1933, as amended (the “Act”), the prospectus included in the Registration Statement (the “Base Prospectus”) and the prospectus supplement dated December 23, 2022 to be filed with the Commission pursuant to Rule 424(b) promulgated under the Act (together with the Base Prospectus, the “Prospectus”). The Shares are to be sold by the Company in accordance with that certain Open Market Sale Agreement, dated August 5, 2020, by and between the Company and Jefferies LLC, as amended by Amendment No. 1 to Open Market Sale Agreement, dated May 5, 2021, and by Amendment No. 2 to Open Market Sale Agreement, dated December 23, 2022 (together, the “Agreement”), as described in the Prospectus. In connection with this opinion, we have examined and relied upon the Registration Statement and the Prospectus, the Agreement, the Company’s certificate of incorporation and the bylaws, each as currently in effect, and originals, or copies certified to our satisfaction, of such records, documents, certificates, memoranda and other instruments as in our judgment are necessary or appropriate to enable us to render the opinion expressed below. In rendering this opinion, we have assumed the genuineness of all signatures; the authenticity of all documents submitted to us as originals; the conformity to originals of all documents submitted to us as copies; the accuracy, completeness and authenticity of certificates of public officials; and the due authorization, execution and delivery by all persons other than the Company of all documents where authorization, execution and delivery are prerequisites to the effectiveness thereof. As to certain factual matters, we have relied upon a certificate of an officer of the Company and have not independently verified such matters. We have assumed (i) that each sale of Shares will be duly authorized by the Board of Directors of the Company, a duly authorized committee thereof or a person or body pursuant to an authorization granted in accordance with Section 152 of the General Corporation Law of the State of Delaware (the “DGCL”), (ii) that no more than 50.0 million Shares will be sold under the Agreement pursuant to the Prospectus and (iii) that the price at which the Shares are sold will equal or exceed the par value of the Common Stock. We express no opinion to the extent that future issuances of securities of the Company, anti-dilution adjustments to outstanding securities of the Company and/or other matter cause the number of shares of Common Stock issuable under the Agreement to exceed the number then available under the Company’s certificate of incorporation. Our opinion herein is expressed solely with respect to the DGCL. Our opinion is based on these laws as in effect on the date hereof. We express no opinion to the extent that any other laws are applicable to the December 23, 2022 Page Two Cooley LLP 3 Embarcadero Center 20th Floor San Francisco, CA 94111-4004 t: (415) 693-2000 f: (415) 693-2222 cooley.com subject matter hereof and express no opinion and provide no assurance as to compliance with any federal or state securities law, rule or regulation. On the basis of the foregoing, and in reliance thereon, we are of the opinion that the Shares, when sold and issued against payment therefor in accordance with the Agreement, the Registration Statement and the Prospectus, will be validly issued, fully paid and nonassessable. We consent to the reference to our firm under the caption “Legal Matters” in the Prospectus and to the filing of this opinion as an exhibit to the Company’s Current Report on Form 8-K filed with the Commission on the date hereof and incorporated by reference into the Registration Statement. In giving such consent, we do not thereby admit that we are in the category of persons whose consent is required under Section 7 of the Act, or the rules and regulations of the Commission thereunder. Sincerely, Cooley LLP By: /s/ Chadwick L. Mills Chadwick L. Mills