AMENDMENT NO. 1 TO AGREEMENT AND PLAN OF MERGER

EXHIBIT 2.1

ANNEX E

AMENDMENT NO. 1 TO
AGREEMENT AND PLAN OF MERGER

     THIS AMENDMENT NO. 1, dated as of December 21, 2006 (this " Amendment "), to the Agreement and Plan of Merger (the " Merger Agreement "), dated as of October 30, 2006, by and among Merck & Co., Inc., a New Jersey corporation (" Parent "), Spinnaker Acquisition Corp., a Delaware corporation and a wholly-owned subsidiary of Parent (" Merger Sub ") and Sirna Therapeutics, Inc., a Delaware corporation (the " Company "). Capitalized terms used herein but not otherwise defined shall have the meanings ascribed to such terms in the Merger Agreement.

WHEREAS, Parent, Merger Sub and Sirna entered into the Merger Agreement; and

     WHEREAS, Parent, Merger Sub and Sirna each desire to amend the Merger Agreement as provided herein;

     NOW, THEREFORE, in consideration of the mutual agreements specified in this Amendment, Parent, Merger Sub and Sirna each agree as follows:

     1. The words "four business days" in Section 7.2(b)(y)(