Exhibit 99.1

                 THIRD AMENDMENT TO LOAN AND SECURITY AGREEMENT
                                     BETWEEN
                                 HYBRIDON, INC.
                                       AND
                               SILICON VALLEY BANK


         This  Third  Amendment  is  made,  effective  as of  the  18th  day  of
September,  1998 to that certain Loan and Security  Agreement  between Hybridon,
Inc., a Delaware  corporation  with a principal place of business at 155 Fortune
Boulevard, Milford,  Massachusetts (the "Borrower") and Silicon Valley Bank (the
"Bank")  dated as of December 31, 1996, as amended by consent  letter  agreement
(the "Consent  Letter")  dated  January 15, 1998 and by First  Amendment to Loan
Security  Agreement  dated  March 30, 1998 (the  "First  Amendment")  and Second
Amendment  to Loan and  Security  Agreement  dated April 16,  1998 (the  "Second
Amendment").  The Loan and  Security  Agreement  as so  amended  is  hereinafter
referred to as the "Loan Agreement."  Capitalized terms used, but not defined in
this  Third  Amendment  shall  have the  meanings  ascribed  to them in the Loan
Agreement and ancillary  documents,  instruments  and  agreements,  or if not so
defined,  shall have the  meanings  ascribed to them in the  Uniform  Commercial
Code,  or in the case of financial and  accounting  terms,  in  accordance  with
generally accepted accounting principles.

                                    RECITALS

         Pursuant  to the Loan  Agreement  and on the terms and  conditions  set
forth  therein,  on December 31, 1996,  the Bank made a secured term loan to the
Borrower in the original  face amount of $7,500,000  (the "Loan").  The Borrower
advised the Bank of its planned  offering of Units of investment in the Borrower
in January, 1998 (the "Original  Offering"),  which was consented to by the Bank
pursuant  to the  Consent  Letter  and which  was  subsequently  amended  by the
Borrower  and  consented  to by the Bank in March,  1998  pursuant  to the First
Amendment  and in  April,  1998  pursuant  to the  Second  Amendment.  The  term
"Offering" as used in this Third Amendment shall include the amended Offering or
any other equity offering or corporate  collaboration not involving indebtedness
of the Borrower.  In connection with the Borrower's  continuing  sales of equity
interests and on the terms and  conditions  set forth  herein,  the Borrower has
requested that the Bank  temporarily  waive  compliance by the Borrower with the
application of the Minimum Liquidity and Tangible Net Worth covenants.

         The Bank is willing to consent  to a  temporary  waiver of the  Minimum
Liquidity  and  Tangible  Net  Worth  covenants,  but only  upon the  terms  and
conditions set forth in this Third Amendment.

                                    AGREEMENT

         In  consideration  of  the  foregoing,  and  of  the  undertakings  and
obligations of the Borrower and the Bank set forth herein and for other good and
valuable   consideration,   receipt   and   sufficiency   of  which  are  hereby
acknowledged, the Borrower and Bank agree as follows:

     1.   The Borrower  confirms that the  outstanding  balance of principal and
          interest  on the Loan as of  September  18th,  1998 is as set forth in
          Schedule 1 hereto,  and that the  Borrower  has no  defense,  claim or
          offset which would preclude full payment of such amount.





     2.   The Borrower  ratifies and confirms:  (i) its  Obligations to the Bank
          under  the  Loan  Agreement,  as  amended  hereby,  (ii)  all  of  the
          representations  and  warranties  made  by it in the  Loan  Agreement,
          except as  expressly  disclosed  to the Bank,  and (iii) that it is in
          compliance  with the  covenants and  agreements  contained in the Loan
          Agreement  except for its  failure  to  maintain  compliance  with the
          covenants  waived in the First  Amendment,  its failure to comply with
          Section 6.10(c) of the Loan Agreement, to the extent that such failure
          is nevertheless in compliance with the Intellectual  Property Security
          Agreement (the "IP Security  Agreement")  delivered by the Borrower in
          connection   with  the  Consent  Letter  (it  being  agreed  that  the
          provisions  of  Section  6.10(c)  shall be  deemed  superseded  by the
          analogous  provisions  of the IP Security  Agreement),  and except for
          Borrower's  failure to comply with the Minimum  Liquidity and Tangible
          Net Worth covenants as of June 30, 1998 and thereafter.

     3.   On  August  7,  1998,  the  Borrower   established  with  the  Bank  a
          certificate of deposit in the amount of $1,592,386 (the "Deposit"). On
          the date of this Amendment,  the Borrower authorizes the Bank to apply
          the Deposit against the outstanding  principal of the Obligations as a
          permanent reduction therein.  Such payment is in addition to any other
          regularly scheduled payments due under the Loan Agreement.

     4.   The Bank hereby waives any existing  defaults of the Minimum Liquidity
          and Tangible Net Worth  covenants  and also waives  compliance  by the
          Borrower with the Minimum  Liquidity and Tangible Net Worth  covenants
          through  September  29, 1998;  provided,  however that if the Borrower
          earlier  receives  the  cash  payment  due to it for  its  sale of its
          partnership  interest (the "CRLP  Interest") in Charles River Building
          Limited  Partnership  (such  date of  receipt,  the "CRLP Put  Date"),
          testing of such  covenants  shall begin on the following  business day
          after the CRLP Put Date rather than on September 30, 1998.

     5.   Section 6.8 of the Loan Agreement,  as previously  amended,  is hereby
          amended in its entirety to read as follows:

               "Borrower shall  maintain,  as of the last day of each quarter of
               Borrower's fiscal year, a Tangible Net Worth of not less than Six
               Million Dollars ($6,000,000.00)."

     6.   Section 6.9 of the Loan Agreement,  as previously  amended,  is hereby
          amended in its entirety to read as follows:

               "Borrower  shall  maintain  Minimum   Liquidity  (as  hereinafter
               defined) of at least $4,000,000 as of the fifteenth (15th) and as
               of the last day of the month (or the next  business day if either
               is not a business day). If the Borrower fails to maintain Minimum
               Liquidity at any test date, the Borrower shall  immediately repay
               the then outstanding  Obligations in full. "Minimum Liquidity" is
               defined as consolidated cash on hand (other than cash in which an
               entity  other  than  the  Bank  or its  assignee  has a  security
               interest, and other than the CRLP Withhold), cash equivalents and
               marketable securities,  plus 50% of the Borrower's Trade Accounts
               Receivable. "Trade Accounts Receivable" means accounts receivable
               arising from the sale of goods and services and the  licensing of
               technology in the ordinary course of the Borrower's business, but
               excluding the


                                        2





          extraordinary sale of assets or other transactions not in the ordinary
          course of the Borrower's business."

     7.   Within two (2)  business  days after the CRLP Put Date,  the  Borrower
          will pay to the Bank in good and collected  funds,  in addition to any
          regularly  scheduled payments on the Obligations,  the sum of $750,000
          as an additional  payment  against the  principal of the  Obligations.
          Until  payment  of such  sum to the  Bank,  all  proceeds  of the CRLP
          interest received shall be held in trust by the Borrower for the Bank.
          The Borrower and the Bank agree that this  requirement  supersedes any
          requirement  contained in the Loan Agreement,  as previously  amended,
          relating to funds  received by the Borrower from CRLP or its partners,
          including,  without  limitation,  any requirement as to the use of the
          proceeds of such funds.

     8.   Conditioned  upon  satisfaction of the  requirements set forth in this
          paragraph,  the Bank consents to the exclusive license by the Borrower
          to OriGenix Therapeutics,  Inc., a Quebec corporation ("OriGenix"), of
          the specific patents and applications listed in Schedule 8 hereto (the
          "Patents"),  which  license shall be limited to use of the Patents for
          the  development  of treatments  for Human  Papilloma  Virus  ("HPV"),
          Hepatitis  B  Virus  ("HBV")  and up to  three  (3)  additional  viral
          indications to be agreed upon among OriGenix and the Borrower, subject
          to  the  prior  written   consent  of  the  Bank  which  will  not  be
          unreasonably withheld (collectively, the "Indications").  The Borrower
          will  retain  the  rights  to the  Patents  for other  indication  and
          molecular  targets.  The  Bank  agrees  to  deliver  to  the  Borrower
          documents  necessary  to (i)  release  its  security  interest  in the
          patents and  applications  listed in  Schedule 8 which are  designated
          with the 189 and 190 suffixes,  and (ii)  subordinate,  pursuant to an
          agreement  acceptable  to the  Borrower  and  OriGenix,  its  security
          interest to the  exclusive  licenses  to be granted to  OriGenix  with
          respect  to  all of the  other  patents  and  applications  listed  in
          Schedule 8. The  consents,  release and  subordinations  referenced in
          this paragraph are conditioned  upon (a) the Borrower  retaining a 40%
          equity ownership in OriGenix,  (b) the Borrower granting to the Bank a
          perfected,  first priority  security interest in the Borrower's entire
          ownership  interest in OriGenix  pursuant to a Pledge Agreement in the
          form of Exhibit 8, (c) OriGenix being  capitalized with a minimum cash
          equity  investment of CDN  $4,000,000  from  investors  other than the
          Borrower,  and (d) the Borrower  warranting and  representing  that no
          investor in OriGenix  owns more than five (5%) percent of the stock of
          the Borrower on a fully converted basis. The Borrower shall,  prior to
          the Bank's  delivery of the  releases  and  subordinations  referenced
          above, make a best efforts attempt to provide the Bank in writing with
          the names and  addresses of the  investors in the new entity and their
          respective ownership  interests,  a complete copy of any prospectus or
          offering  memorandum  provided to  investors,  a complete  copy of the
          business  plan for the new entity and such  other  information  as the
          Bank may reasonably require,  including evidence of the Borrower's 40%
          interest in OriGenix.

     9.   The Borrower further  acknowledges  that all reasonable  out-of-pocket
          costs  and  expenses  of the  Bank  in  connection  with  negotiation,
          documentation and  administration  of this Third Amendment,  including
          reasonable fees of attorneys  engaged to represent the Bank,  shall be
          borne by the Borrower.


                                        3



     10.  The Borrower  acknowledges  and  confirms  that to the extent that the
          Borrower  may have any claims,  offsets,  counterclaims,  or defenses,
          asserted or unasserted, the Borrower, for itself, and on behalf of its
          successors,   assigns,  parents,  subsidiaries,   agents,  affiliates,
          predecessors,  employees, officers, directors, executors and heirs, as
          applicable  (collectively,  the  "Borrower  Affiliates")  releases and
          forever discharges the Bank, its subsidiaries,  affiliates, employees,
          officers,  directors, agents, successors and assigns, both present and
          former  (collectively,  the "Bank Affiliates") of and from any and all
          manner  of  claims,  offsets,  counterclaims,   defenses,  action  and
          actions,  cause and causes of  action,  suits,  debts,  controversies,
          damages,  judgments,  executions, and demands whatsoever,  asserted or
          unasserted,  in law or in equity,  which  against  the Bank and/or the
          Bank  Affiliates,  they or the  Borrower  Affiliates  ever  had to and
          including  the date  hereof,  upon or by reason of any matter,  cause,
          causes or thing whatsoever,  in connection with the Loan and/or any of
          the  transactions   and  matters  related  thereto,   except  for  the
          obligations of the Bank in such documents,  instruments and agreements
          to be performed after the date of this Third  Amendment.  The Borrower
          shall  indemnify,  defend and hold the Bank  harmless  of and from any
          claim  brought or  threatened  against the Bank by the Borrower or any
          other  person  (as  well as  from  attorneys'  fees  and  expenses  in
          connection therewith) on account of the Loan Agreement,  the Note, the
          Consent Letter, the Intellectual  Property Security Agreement,  Pledge
          Agreement,  Intercreditor  Agreement,  the First Amendment, the Second
          Amendment, this Third Amendment and any other document,  instrument or
          agreement   given  in  connection   with  the  Loan  and  any  of  the
          transactions  and  matters  related  thereto  (each  of  which  may be
          defended, compromised,  settled or pursued by the Bank with counsel of
          the Bank's election reasonably acceptable to the Borrower,  but at the
          expense of the Borrower),  except in the case of the Bank's failure to
          comply  with  its  obligations  hereunder  or  thereunder,  its  gross
          negligence or willful misconduct.

     11.  The Borrower  acknowledges and agrees that the Bank's agreement herein
          to  temporarily  waive  compliance  with  the  Minimum  Liquidity  and
          Tangible Net Worth  covenants  shall not create a course of dealing or
          conduct  and that the Bank has not agreed to waive any other  covenant
          or agreement with the Borrower or to waive compliance with the Minimum
          Liquidity and Tangible Net Worth  covenants other than for the limited
          time period set forth in this Third Amendment.

     12.  To the extent possible,  this Third Amendment shall be construed to be
          consistent with the provisions of the Loan Agreement;  however, to the
          extent that the provisions of this Third Amendment  expressly conflict
          with  or  contradict  the  provisions  of  the  Loan  Agreement,   the
          provisions of this Third Amendment shall be deemed to control.

     13.  This Third  Amendment  represents  the entire  agreement  between  the
          parties with respect to the modifications  contained herein, and shall
          be  construed  in  accordance  with  the laws of the  Commonwealth  of
          Massachusetts as an agreement under seal. The Borrower has voluntarily
          entered into this Third  Amendment  without  coercion or duress of any
          kind and has been or has had the opportunity to have been  represented
          by legal counsel of their choosing.


                                        4



         WITNESS OUR hands and seals on this 18th day of September, 1998.

HYBRIDON, INC.                                           SILICON VALLEY BANK

By:  /s/Robert G. Andersen                      By: /s/ Sean Lynden
     ---------------------                          -------------------------

                                        5



                                  SCHEDULE 1 TO
                 THIRD AMENDMENT TO LOAN AND SECURITY AGREEMENT
                                     BETWEEN
                               SILICON VALLEY BANK
                               AND HYBRIDON, INC.


Principal Balance as of September 15, 1998                    $4,487,175.22
Interest outstanding at September 15, 1998                        23,768.61


                                        6